vani-20241231.htm
UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
DC 20549
FORM
10-K
(Mark
One)
For
the Fiscal Year Ended December 31, 2024
OR
For
the transition period from ________ to ________
Commission
File Number 001-36747
Vivani
Medical, Inc.
(Exact
name of registrant as specified in its charter)
(Address of principal executive offices, including zip code)
Registrant’s
telephone number, including area code: (415) 506-8462
Securities
registered pursuant to Section 12(b) of the Act:
Title of Each Class Trading Symbol Name of Each Exchange on Which Registered
Common Stock, par value $0.0001 per share VANI The NASDAQ Capital Market
Securities
registered pursuant to Section 12(g) of the Act: None
Indicate
by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐No
☒
Indicate
by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Exchange Act. Yes
☐No ☒
Indicate
by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange
Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports),
and (2) has been subject to such filing requirements for the past 90 days.
Yes☒ No ☐
Indicate
by check mark whether the registrant has submitted electronically on its corporate website, if any, every Interactive Data File
required to be submitted and pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months
(or for such shorter period that the registrant was required to submit such files). Yes☒ No ☐
Indicate
by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller
reporting company. See definition of “large accelerated filer,” “accelerated filer,” “smaller reporting
company”, and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☐
If
an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for
complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate
by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness
of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered
public accounting firm that prepared or issued its audit report. ☐
If
securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the
registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate
by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation
received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate
by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐No☒
The
aggregate market value of the shares of the registrant’s Common Stock held by non-affiliates of the registrant as of June 30, 2024, computed by reference to the closing sales price on the Nasdaq Capital Market on June 30, 2024, was approximately $45.1
million.
As
of March 28, 2025, the registrant had 59,242,903 shares of common stock, par value $0.0001 per share.
DOCUMENTS
INCORPORATED BY REFERENCE
Portions
of the registrant’s Definitive Proxy Statement for the 2025 Annual Meeting of Stockholders (the “Proxy Statement”)
are incorporated herein by reference in Part III of this Annual Report on Form 10-K to the extent stated herein. Registrant intends
to file a definitive proxy statement pursuant to Regulation 14A with the Securities and Exchange Commission (the “SEC”)
within 120 days after the end of registrant’s fiscal year end of December 31, 2024.
VIVANI
MEDICAL, INC.
AND
SUBSIDIARIES
FORM
10-K
TABLE
OF CONTENTS
Page
PART I
Item 1. Business 5
Item 1A. Risk Factors 29
Item 1B. Unresolved Staff Comments 59
Item 1C. Cybersecurity 60
Item 2. Properties 61
Item 3. Legal Proceedings 61
Item 4. Mine Safety Disclosures 61
PART II
Item 6. Reserved 62
Item 7A. Quantitative and Qualitative Disclosures about Market Risk 69
Item 8. Financial Statements and Supplementary Data 70
Item 9A. Controls and Procedures 70
Item 9B. Other Information 71
Item 9C. Disclosure regarding foreign jurisdictions that prevent inspections 71
PART III
Item 10. Directors, Executive Officers and Corporate Governance 72
Item 11. Executive Compensation 72
Item 14. Principal Accounting Fees and Services 72
PART IV
Item 15. Exhibits, Financial Statement Schedules 73
SIGNATURES 76
SUMMARY
OF RISK FACTORS
Below
is a summary of the principal risk factors related to the Annual Report on Form 10-K (“Form 10-K”) for the fiscal
year ended December 31, 2024.
Our
business is subject to a number of risks of which you should be aware before making an investment decision. These risks are discussed
more fully in the “Risk Factors” section of this Form 10-K. These risks include, but are not limited to, the following:
CAUTIONARY
NOTE REGARDING FORWARD-LOOKING STATEMENTS
AND
FACTORS THAT MAY AFFECT FUTURE RESULTS
This Form 10-K, includes forward-looking statements within the meaning of Section 27A of the Securities
Act of 1933, as amended (the “Securities Act”) and Section 21E of the Securities Exchange Act of 1934, as amended the (“Exchange
Act”). All statements other than statements of historical fact contained in this Form 10-K are forward-looking statements. In some
cases, you can identify forward-looking statements by terminology such as “may,” “could,” “will,”
“would,” “should,” “expect,” “plan,”, “anticipate,” “believe,”
“estimate,” “intend,” “predict,” “seek,” “contemplate,” “project,”
“continue,” “potential,” “ongoing” or the negative of these terms or other comparable terminology,
although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are
not limited to, statements about:
● our ability to create and maintain a pipeline of product candidates;
Any
forward-looking statements in this Form 10-K reflect our current views with respect to future events or to our future financial
performance and involve known and unknown risks, uncertainties, assumptions and other factors described under the “Risk
Factors” section and elsewhere in this Form 10-K, that may cause our actual results, performance or achievements to be materially
different from any future results, performance or achievements expressed or implied by these forward-looking statements. Given
these uncertainties, you should not place undue reliance on these forward-looking statements.
In
addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject.
These statements are based upon information available to us as of the date of this report, and while we believe such information
forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be
read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information.
These statements are inherently uncertain, and investors are cautioned not to unduly rely upon these statements as predictions
of future events. Except as required by law, we assume no obligation to update or revise these forward-looking statements for
any reason, even if new information becomes available in the future.
This
Form 10-K also contains estimates, projections and other information concerning our industry, our business, and the markets for
certain diseases, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical
conditions. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently
subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this
information. Unless otherwise expressly stated, we obtained this industry, business, market and other data from reports, research
surveys, studies and similar data prepared by market research firms and other third parties, industry, medical and general publications,
government data and similar sources.
PART
I
Item
1. Business
Our
Company
Company
Overview
Vivani Medical, Inc. (“Vivani,” the “Company,” “we,” “us,” “our” or similar terms) is a clinical stage biopharmaceutical company which develops miniaturized, subdermal drug implants utilizing its proprietary NanoPortalTM technology, which is designed to enable ultra long-acting, near constant-rate delivery of a broad range of medicines to treat chronic diseases. Vivani uses this platform technology to develop and potentially commercialize drug implant candidates, alone or in collaboration with pharmaceutical company partners, to address a leading cause of poor clinical outcomes in the treatment of chronic disease, medication non-adherence. According to the U.S. Centers for Disease Control and Prevention, adherence is defined as the extent to which an individual’s behavior, including taking medications, corresponds to recommendations from a health care provider. An alarmingly high proportion of patients, approximately 50%, do not take their medicine as prescribed in the real world, a statistic that applies to both daily oral as well as weekly injectable medicines. For example, a recent study has shown that 64% of patients taking Wegovy® (semaglutide injection) discontinue therapy within the first year of treatment, a number that increases to 76% by the second year. Unfortunately, GLP-1 discontinuation may result in a quick reversal of the health benefits in the majority of patients.
At Vivani, we are developing a portfolio of miniature, subdermal drug implant candidates that, unlike most oral and injectable medicines, are designed with the goal of guaranteeing medication adherence by delivering therapeutic drug levels for up to six months or longer. In addition, our aim is to minimize fluctuations in patients’ drug levels through the use of our NanoPortal technology, which may improve the tolerability profiles for medicines, including GLP-1 receptor agonists, that produce side effects associated with fluctuating drug levels in the blood.
We believe our emerging portfolio of miniature, ultra long-acting drug implants has the potential to revolutionize the treatment of chronic diseases by directly addressing poor medication adherence and improving patient tolerability to their treatments which has the potential to translate into better health outcomes for patients in the real-world setting. Vivani's lead programs include NPM-115 (high-doseexenatide) and NPM-139 (semaglutide). These miniature, subdermal, GLP-1 implants are under development for chronic weight management in obese and overweight individuals with once or twice-yearly dosing.ent NPM-115, is a miniature, six-month, GLP-1 (high-dose exenatide) implant currently in clinical-stage testing for chronic weight management in obese and overweight individuals. This first-in-human clinical study, also called LIBERATE-1TM, is being conducted in Australia and is anticipated to report top-line data in mid-2025. NPM-139, a semaglutide implant, also in development for the treatment of chronic weight management, is currently in preclinical-stage development and has recently generated encouraging preclinical weight loss data. NPM-139 has the added potential benefit of once-yearly dosing.
Other programs include, NPM-119 (exenatide implant) in development for the treatment of type 2 diabetes and OKV-119, another GLP-1 based implant in development for the treatment of cardiometabolic disorders in cats in collaboration with animal health partner Okava Pharmaceuticals, Inc. (“Okava”). Finally, the company is also considering the development of a semaglutide implant for the treatment of type 2 diabetes.
Vivani resulted from the business combination of Second Sight Medical Products, Inc. (“Second Sight”) and Nano Precision Medical, Inc. (“NPM”). On August 30, 2022, Second Sight and NPM completed their merger pursuant to which NPM became a wholly owned subsidiary of Second Sight and the combined company of NPM and Second Sight was renamed Vivani Medical, Inc. Vivani’s main priority is the further development of its lead programs NPM-115 (exenatide implant) and NPM-139 (semaglutide implant) for chronic weight management in obese or overweight patients with one or more risk factors and further development of the balance of the company’s miniature, ultra long-acting drug implant portfolio. In parallel, Vivani’s management team remains committed to identifying and exploring strategic options that will enable further development of its pioneering neurostimulation systems from legacy company Second Sight aimed at helping patients recover critical body functions.
In December 2022, we contributed our neurostimulation assets from legacy company Second Sight and certain liabilities to Cortigent, Inc. (“Cortigent”), a wholly owned subsidiary of Vivani to advance the Company’s pioneering neurostimulation technology. Cortigent has 5,000,000 shares of common stock outstanding, all owned by Vivani. In March 2023, Vivani announced the filing of a Registration Statement on Form S-1 with the U.S. Securities and Exchange Commission (“SEC”) for a proposed initial public offering of Cortigent. In March 2025, Vivani announced a change in strategy to discontinue efforts to pursue a proposed initial public offering and shift focus to file a Form 10 with the SEC to support the spin-off of Cortigent into a fully independent, publicly traded company. The strategic goal of this transaction is to create two focused companies dedicated to driving current and future value in their respective therapeutic areas of expertise.
On July 6, 2023, Vivani changed its state of incorporation from the State of California to the State of Delaware by means of a plan of conversion, effective July 5, 2023. The reincorporation, including the principal terms of the plan of conversion, was submitted to a vote of, and approved by, Vivani’s stockholders at its 2023 Annual Meeting of Stockholders held on June 15, 2023. As part of this change of incorporation the Company established a par value of $0.0001 per share and all periods have been retroactively adjusted to reflect this change. If the spinoff is successful, the loan
payable from Cortigent to Vivani would be forgiven.
An Investigational New Drug ("IND") application for NPM-119 (GLP-1 implant) was submitted to the FDA on July 14, 2023, to support the initiation of a first-in-human study of an exenatide implant in patients with type 2 diabetes. On August 18, 2023, FDA provided written notification that the study was on full clinical hold, primarily due to insufficient Chemistry, Manufacturing, and Controls (“CMC”) information to assess the risk to human subjects. After providing additional information to sufficiently address the FDA's requests, the FDA lifted the clinical hold on NPM-119 on June 13, 2024 allowing for the proposed study to proceed. The primary objective of this first-in-human clinical study was to evaluate the safety, tolerability and pharmacokinetics of NPM-119 in type 2 diabetes patients. The initial study design also incorporated Bydureon BCise® (exenatide injection) for comparison purposes.
On
August 25, 2023, the Company and Cortigent entered into an Amendment 1 (the “Amendment”) to the Transition Funding, Support
and Services Agreement dated March 19, 2023 (the “TFSSA”). Pursuant to the
TFSSA, Vivani has agreed to advance funds and provide or cause to be provided
to Cortigent the services and funding intended to cover salaries and related
costs, rent and other overhead in order to permit Cortigent to operate in
substantially the same manner in which business operations of Cortigent were
previously operated by Second Sight, prior to the formation of Cortigent, which
obligations will continue, in the case of the funding obligations, at the discretion of Vivani or after the closing of an initial public offering of
Cortigent. If an initial public offering of Cortigent closes, Cortigent has
agreed to repay $1,500,000 to Vivani and enter into a five-year promissory note at 5% interest for $2,000,000
in favor of Vivani. Consequently, Vivani will forgive any remaining amounts due
by Cortigent. Efforts to support a successful initial public offering of Cortigent ceased in March 2025 and efforts are now focused on a potential spinoff with the filing of a Form 10 registration statement. The TFSSA terminated effective December 31, 2024.
In
the fourth quarter of 2023, Vivani Medical
Australia Pty Ltd., a wholly owned subsidiary in Australia, was established to
support studies of our product candidates.
On February 28, 2024, Vivani announced positive preclinical weight loss data with its
exenatide implant that was comparable to semaglutide, the active
ingredient in Ozempic and Wegovy, and a strategic
shift to prioritize the Company's obesity portfolio. In a study of
high-fat diet-induced obese mice, the exenatide implant generated
weight loss of approximately 20% compared to a
sham implant control after a 28-day treatment
duration, comparable to the extent of weight loss observed in mice treated with
semaglutide injections in the same study. In addition, the Company also disclosed that semaglutide is the active
pharmaceutical ingredient in NPM-139, another
miniature, ultra long-acting, subdermal GLP-1 implant in
development for chronic weight management further demonstrating our
prioritization on obesity. NPM-139 also has the
added potential benefit of once-yearly administration.
On
March 1, 2024, the Company entered into a securities purchase agreement
(“Securities Purchase Agreement”) with an institutional investor to purchase 3,947,368 shares of common stock, par value $0.0001 per share (the “Common Stock”) and warrants to
purchase up to an aggregate of 3,947,368 shares
of common stock at a purchase price of $3.80 per
share and accompanying warrant in a registered direct offering (the
“Offering”). The warrants have an exercise price of $3.80
per share, are exercisable immediately upon issuance, and will expire three years following the date of issuance.
On
April 22, 2024, the Company entered into an Open Market Sale AgreementSM
(the “Sales Agreement”) with Jefferies LLC (“Jefferies”), under which the
Company may offer and sell, from time to time at its sole discretion, shares of
the common stock, having an aggregate offering price of up to $75.0 million through Jefferies as its sales agent. Also
on April 22, 2024, the Company filed a Registration Statement on Form S-3, which was declared effective on May 3, 2024,
including a sales agreement prospectus relating to the offering of up to $75.0 million shares of its common stock in accordance
with the Sales Agreement.
On
May 28, 2024, Vivani announced the publication of positive weight loss
data supporting the potential veterinary use of OKV-119, the company's miniature, long-acting GLP-1 implant under development with partner
Okava for the treatment of
pre-diabetes, diabetes and obesity in companion felines. The device is intended
to be conveniently inserted under the skin during routine veterinary visits and
is being designed to deliver six months of
GLP-1 therapy with a single administration.
As
stated previously, on June 13, 2024, Vivani announced that the FDA cleared
the IND and lifted the clinical hold for NPM-119,
the Company's miniature, six-month GLP-1 implant under development for the treatment of
patients with type 2 diabetes.
On
July 11, 2024, the Company provided an update of the clinical development plans
for NPM-115, the clinical program associated with
the miniature, long-acting GLP-1 (high-dose
exenatide) implant for chronic weight management in obese and overweight
individuals. The Company redesigned the first-in-human study, LIBERATE-1, initially intended to explore the safety,
tolerability and pharmacokinetics of its exenatide implant in patients with
type 2 diabetes, to evaluate the implant in obese
and overweight patients.
On
September 4, 2024, Vivani announced positive preclinical liver fat results with
its miniature, ultra long-acting GLP-1 implant currently under development for chronic weight management in obese and overweight individuals and type 2
diabetes. The Company's GLP-1 (exenatide) implant produced sham-implant
adjusted liver fat reduction of 82% in an obese
mouse model from a single administration with expected twice-yearly dosing.
These liver fat data are consistent with published results from similar
investigations with semaglutide, the active pharmaceutical ingredient in
Ozempic and Wegovy.
On
September 26, 2024, the Company reported receiving regulatory approval to
initiate its first-in-human clinical trial with a miniature, ultra long-acting
GLP-1 (exenatide) implant in obese and overweight individuals in Australia.
This clinical trial, known as LIBERATE-1TM , is part of the NPM-115 program and
will investigate the safety, tolerability and full pharmacokinetic profile of
an exenatide implant. The trial also represents the first clinical application
of the Company’s proprietary NanoPortal drug implant technology. LIBERATE-1TM was redesigned to enroll participants who will be titrated on weekly semaglutide
injections for 8 weeks (0.25 mg/week for 4 weeks
followed by 0.5 mg/week for 4 weeks) before being randomized to receive a
single administration of Vivani’s exenatide implant (n=8), weekly exenatide
injections (n=8), or weekly 1 mg semaglutide injections (n=8) for a 9-week treatment duration. Changes in weight will be
measured.
On November 8, 2024, the Company entered into a private sale transaction with one of its independent directors whereby the Company sold an aggregate of 3,968,253 shares of the Company’s common stock to the director at a price of $1.26 per share, which was the lower of the closing price of the Company’s common stock on the Nasdaq or the 5-day average closing price of the Company’s common stock on the Nasdaq, each immediately prior to the closing date, subject to adjustment for reverse and forward stock splits, stock dividends, stock combinations and other similar transactions of the common stock that occur after the date of the private sale transaction. The gross proceeds from this private sale transaction were $5.0 million.
On December 19, 2024, Vivani announced that
screening and enrollment of LIBERATE-1TM, the first-in-human
clinical trial with its NPM-115 program GLP-1 implant in obese and overweight
patients, was initiated at two study centers in Australia. Study results are anticipated to be reported in
mid-2025. On March 13, 2025, Vivani announced the successful administration of its first GLP-1
(exenatide) implant in the LIBERATE-1 clinical trial. The Company also announced full enrollment in the
LIBERATE-1 study, which was achieved in just four weeks after enrollment of the
first subject, signaling early potential interest for this miniature, six-month, subdermal
GLP-1 implant and reaffirming previous estimates that top-line LIBERATE-1 results should
be available in mid-2025.
On March 26, 2025, the Company entered into a private
sale transaction with an entity affiliated with one of its independent
directors whereby the Company shall sell an aggregate of 7,366,071 shares of
the Company’s common stock to the entity, in one or more closings as provided
in the purchase agreement, at a price of $1.12 per share, which was the closing
price of the Company’s common stock on the Nasdaq, subject to adjustment for
reverse and forward stock splits, stock dividends, stock combinations and other
similar transactions of the common stock that occur after the date of the
private sale transaction. The gross proceeds from this private sale transaction
will be approximately $8.25 million.
Our
Proprietary NanoPortal Implant Technology
Vivani’s
implant technology, which we refer to as NanoPortal, utilizes a space-efficient design that allows a miniaturized implant to provide
many months of therapeutic delivery of potent molecules. The technology has no moving parts, which is intended to minimize fluctuating
drug delivery over the duration of the implant and is also tunable. Vivani has primarily been developing implant candidates around
peptide therapeutics, but the technology has potential application across a wide range of molecular types. The key innovative
component of the technology is a biocompatible titanium-oxide nano-porous membrane which consists of millions of precisely sized
nanotubes whose inner diameters represent the only path for drug molecules to exit the reservoir once the implant is fully assembled.
We
believe the key to the technology’s ability to achieve near constant release of drug without moving parts is the ability
to precisely tune the inner diameter of the nanotubes to the same size range as individual drug molecules. If the inner diameter
of the nanotubes is smaller than the size of a given drug molecule, there would be no release at all. If the inner diameter of
the nanotubes is much larger than the size of a given drug molecule, the rate at which the drug leaves the reservoir would follow
traditional physics and would decrease over time as the drug concentration decreases. However, when the opening is close enough
in size to the drug molecules, the drug release is constrained and can result in a variety of desirable delivery profiles, including
near constant release. Vivani’s NanoPortal technology has demonstrated near constant release in an animal model for six
months.
For
drug molecules with adequate potency and stability, NanoPortal can allow minimization of the implant size while extending implant
duration. A custom delivery profile can also be achieved by adjusting the number of accessible nanotubes, engineering changes
to the implant, and/or changes in formulation parameters. With the design flexibility afforded by the NanoPortal technology, Vivani
plans to develop a portfolio of drug implant candidates aimed at addressing chronic diseases with high unmet medical need.
Vivani’s
NanoPortal technology has demonstrated near constant in vitro release for two dose configurations (see left portion of
the chart below). In vitro testing was performed at 37°C on implant devices stored in a buffer solution adjusted to
a physiological pH of 7.4. For a high-dose configuration, the observed near-constant release was demonstrated over the 12-week
measurement period, after which the drug began to be depleted. For a low-dose configuration, the observed near-constant release
lasted for 24 weeks. In addition, the near-constant in vitro release observed has been shown to translate into sustained
exposure levels in vivo over a 6-month duration in an animal model (depicted in the chart below entitled "6-month NPM-119 Prototype (N=6)"). Finally, NanoPortal
has demonstrated minimal in vitro fluctuations during 2.5-hour interval sampling periods which demonstrates a very
smooth release profile (see right portion of the chart below entitled "Near-Constant and Minimally-Fluctuating Release" for individual device release rates). For clarity, the Day 98-100 period was selected to ensure the 2.5 hour variability results were representative of steady-state conditions.
Vivani believes its proprietary NanoPortal implant technology has potential to revolutionize the treatment of chronic diseases by addressing two important limitations of oral and injectable therapies, namely, poor real-world medication adherence, and, in the case of GLP-1 therapy, the potential to improve gastrointestinal tolerability. We believe Vivani’s NanoPortal technology, which is specifically designed and tested to deliver regular and controlled exenatide release, may overcome these challenges. Our NanoPortal implant technology has no moving parts that could otherwise contribute to variations in drug release rates. NanoPortal has demonstrated the ability to release exenatide with minimal fluctuationsin vitro as evidenced by the 2.5-hour release rates shown in the NanoPortal Implant Technology section above. Since the half-life of exenatide in humans is 2.4-4 hours, steady release from one 2.5-hour interval to the next is expected to be associated with minimal device-related exposure fluctuations, potentially minimizing the opportunity for gastrointestinal events.
To address medication adherence, the Company’s NanoPortal implants are designed to provide steady dosing from a single miniature, subdermal device for six months or longer. Current GLP-1 products are associated with only 50-60% real-world medication adherence. Non-adherent patients do not receive the full potential benefits of existing treatments. For example, medication non-adherence for patients with type 2 diabetes is associated with approximately $5,500 per non-adherent patient in avoidable healthcare costs associated with unnecessary acute care and hospitalization visits. The NanoPortal technology can enable ultra long-acting dosing, up to 6 months or longer, which can directly address the medication adherence challenge.
A well-documented side effect of the GLP-1 class is poor gastrointestinal (“GI”) tolerability. GI intolerance can present as nausea, vomiting, and/or diarrhea which can lead to volume loss, acute kidney injury (“AKI”) and potentially major cardiovascular adverse events. GI-related issues are the most commonly reported side effect for all drugs in the GLP-1 class. In responding to a marketing application filed for Intarcia's ITCA 650 exenatide implant candidate, with a proposed indication for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (“T2DM”), the FDA stated in a July 29, 2022 letter that they believe marked increases in the dose of a GLP-1 are responsible for increased risk of GI intolerance and combined with the daily in vitro variability exhibited by ITCA 650 resulted in the FDA summarizing their findings as follows: “the clinical data in the three pivotal clinical trials for ITCA 650–including the high rates of nausea, vomiting, and diarrhea, the high rates of discontinuations due to these adverse gastrointestinal reactions, and most notably, the increased risk of AKI comprise safety signals whose root cause can reasonably be concluded to be irregular and uncontrolled exenatide release” and “The data provided to validate the limits of the in vitro dose delivery specifications did not support the safe and effective use of the device constituent of ITCA 650.”
We believe Vivani’s NanoPortal technology, which is specifically designed and tested to deliver regular and controlled exenatide release, may overcome these challenges. Our NanoPortal implant technology has no moving parts that could otherwise contribute to variations in drug release rates. NanoPortal has demonstrated the ability to release exenatide with minimal fluctuations in vitro as evidenced by the 2.5-hour release rates shown in the NanoPortal Implant Technology section above. Since the half-life of exenatide in humans is 2.4-4 hours, steady release from one 2.5-hour interval to the next is expected to be associated with minimal device-related exposure fluctuations, potentially minimizing the opportunity for gastrointestinal events.
Evidence to support non-fluctuating drug release afforded by Vivani’s NanoPortal technology compared to the drug release profile of the ITCA 650 osmotic pump technology is provided in the schematic below. Although head-to-head testing was not conducted, the left panel shows, the in vitro daily release profiles for the 4 ITCA 650 devices with the highest day-to-day variability of the 12 total devices tested. The ITCA 650 device data was presented by FDA at the September 28, 2023. FDA Open Public Hearing to review the approvability of Intarcia Therapeutic’s ITCA 650 (exenatide implant). The right panel shows the in vitro daily release profiles for the 4 NanoPortal devices with the highest day-to-day variability of the 17 total devices tested by Vivani.
Preliminary market research regarding the potential adoption and market penetration of Vivani's emerging drug implant candidates has been encouraging. For example, during FDA’s Open Public Hearing on September 28, 2023 to review Intarcia's ITCA 650 (exenatide implant), the independent firm dQ&A Market Research reported results from a patient preference study testing a product profile reflective of both ITCA 650 and NPM-119 (e.g. miniature, six-month, subdermal, GLP-1 implant). Of the 324 patients currently on GLP-1 therapy, 56% indicated either “Definitely” or “Likely” when asked about the likelihood of getting and using a GLP-1 implant if it was approved by FDA, recommended by their healthcare provider, and covered by insurance.
For example, results from a small, third-party market research study funded by Vivani indicate that the majority of physicians would be highly likely to recommend a product with the NPM-119 target product profile to their type 2 diabetes patients. In this market research study, primary care physicians (n=10) provided an average rating of 8.3 out of 10 in terms of likelihood of recommending a product with NPM-119’s target product profile. Although additional market research will be conducted as Vivani's drug implant candidates progress in development, these early signals regarding product adoption indicate significant market opportunity and a highly differentiated, convenient, alternative GLP-1 treatment option for patients, healthcare providers, and payers.
Our
Emerging Portfolio
Although
Vivani’s proprietary NanoPortal implant technology may potentially be broadly applied across a wide range of therapeutic
molecules and disease areas, our initial focus is on peptide therapeutics for the treatment of patients with metabolic disease.
The pipeline table below depicts our current portfolio of four distinct pre-clinical stage programs targeting type 2 diabetes
(in humans and companion cats), and obesity/chronic weight management
Below
is a summary description of each pipeline program:
NPM-115:
This high-dose exenatide implant candidate is in clinical stage development for the treatment of chronic weight management
in patients with obesity or overweight. Obesity is a global epidemic with over 1 billion adults and children currently living with obesity globally. The global prevalence of obesity has more than tripled since 1975. Today, less than 5% of these people are medically treated. Obesity affects both the individual and society at large. Obesity is associated with over 200 health complications and is associated with an increasing proportion of healthcare costs.
Leveraging the ultra long-acting six-month dosing regimen, the Company will also be exploring the potential for NPM-115 to provide maintenance therapy for patients who have previously lost weight on other injectable or oral GLP-1 therapies, including dual or triple incretin products. This differentiated treatment approach could provide patients, caregivers and healthcare professionals the convenience of a miniature, twice-yearly, subdermal GLP-1 implant that is administered during a routine office visit.
Vivani received regulatory approval and has subsequently initiated its first-in-human clinical trial for the NPM-115 program in obese and overweight individuals in Australia. This clinical trial, known as LIBERATE-1TM, will investigate the safety, tolerability and full pharmacokinetic profile of an exenatide implant leveraging the Company’s proprietary NanoPortal drug implant technology. LIBERATE-1 is designed to enroll participants who will be titrated on weekly semaglutide injections for 8 weeks (0.25 mg/week for 4 weeks followed by 0.5 mg/week for 4 weeks) before being randomized to receive a single administration of Vivani’s exenatide implant (n=8), weekly exenatide injections (n=8), or weekly 1 mg semaglutide injections (n=8) for a 9-week treatment duration. Although not the primary objective of LIBERATE-1, changes in weight will also be measured. The trial was initiated at the end of 2024 with data projected to be available in mid-2025.
Vivani believes that higher doses of exenatide, compared to those exenatide doses currently approved to treat type 2 diabetes, can achieve similar weight loss effects
as other GLP-1 products. This belief is based on the fact that semaglutide injection was originally approved at doses up to 1.0mg/week to treat type 2 diabetes (Ozempic) while semaglutide injections for chronic weight management (Wegovy) required higher doses up to 2.4mg /week to maximize weight loss effects of the treatment.
In both the treatment of obesity and type 2 diabetes, GLP-1 products have challenges associated with medication adherence
and persistence which can lead to sub-optimal patient outcomes. As shown in the graph below, results from a large, retrospective
cohort study published in the research journal Obesity show improved medication persistence with the newer GLP-1 weight
loss products compared to previous products. That said, the one-year persistence of patients taking semaglutide was still only
40%. This highlights the potential for further improvement for the 60% of individuals who were no longer taking semaglutide after
one year. The potential benefits for a long-term implant like NPM-115 are apparent when considering that body weight begins
to increase shortly after GLP-1 therapy is discontinued.
Preliminary
weight loss data of NPM-115 in preclinical models is encouraging. In a study in high fat diet-induced obese mice, NPM-115 generated
weight loss of approximately 20% compared to a sham implant control after a 28-day treatment duration, comparable to weight loss
observed in mice treated with semaglutide in the same study. The supratherapeutic
doses provided for both NPM-115 (single administration delivering exenatide at ~530 nmol/kg/day), and semaglutide (weekly injections
of ~2,700 nmol/kg/week) were selected to maximize the weight-loss potential of both exenatide and semaglutide.
Emerging data on the durability of effect on weight in animals with an exenatide implant provides confidence that this treatment modality has the potential as a treatment for chronic weight management and potentially, the maintenance of weight loss after obese or overweight individuals have already lost sufficient weight on other GLP-1 monotherapy. The dose configuration of the exenatide implant test article in the ongoing LIBERATE-1 study is expected to be supportive of both the NPM-115 and NPM-119 programs. Additional information supporting the NPM-119 program is provided below.
NPM-139: Semaglutide based products are the largest selling GLP-1 products on the U.S. market today with combined 2024 sales of over $25 billion. NPM-139 (semaglutide implant) is a highly differentiated, GLP-1 product candidate specifically designed to improve medication adherence and, potentially, patient tolerability to their medicine. NPM-139 is in feasibility stage testing and has recently generated encouraging preclinical weight loss data consistent with weight loss reported with semaglutide injections in similar preclinical models (see figure below).
In this ongoing study in healthy rats, a single administration of the semaglutide implant NPM-139 resulted in body weights that were nearly 20% lower than a sham implant control group throughout a 91-day treatment period. Like NPM-119 and NPM-115, NPM-139 has demonstrated smooth, non-fluctuating in vivo release; this was confirmed by pharmacokinetic data from this study which demonstrated continuous and steady semaglutide exposure throughout the study period. NPM-139 has previously demonstrated therapeutic semaglutide exposure levels in pharmacokinetic data over a six-month duration in healthy rats. In vitro chemical and physical stability measurements for durations exceeding one year indicate the potential for once-yearly administration of NPM-139. Together, these data demonstrate the versatility of the NanoPortal technology beyond NPM-115 (exenatide implant) and provide significant encouragement for continued development of each program.
NPM-119:
This exenatide implant candidate is a miniature, six-month, subdermal GLP-1 implant under development for the treatment of type 2 diabetes. According to the CDC, more than 37 million Americans have diabetes and 90-95% have type 2 diabetes. The total number of people living worldwide with diabetes today is 537 million and is projected to rise to 643 million by 2030 and 783 million by 2045. Of the 537 million people with diabetes today, only 15% have good glycemic control. According to the American Diabetes Association (“ADA”), the total cost of diabetes in the U.S. was $413 billion in 2022, including $307 billion for direct medical costs and $106 billion for reduced productivity in premature mortality. In 2024, global sales of GLP-1 receptor agonists products (all indications) were over $50 billion and are projected to reach over $250B per year by 2034. Because the current drug adherence rate for type 2 diabetes is only 40-60% for oral and injectable GLP-1 products, Vivani believes there is significant unmet need for a GLP-1 implant that could address non-adherence.
NPM-119 was initially intended to support a first-in-human study in patients with type 2 diabetes and has an open IND with a clinical trial that was cleared to proceed by the FDA. This clinical study was temporarily postponed so that Vivani could prioritize the NPM-115 program in development for chronic weight management in obese and overweight individuals. The exenatide implant used in the NPM-115 program is the same configuration intended for use in the initial NPM-119 study. As a result, study results from the initial exenatide implant study, LIBERATE-1, are expected to be supportive for both the NPM-115 and NPM-119 programs. Exenatide is a GLP-1 receptor agonist (GLP-1 RA or GLP-1) and was originally approved as the
twice-daily subdermal injection, Byetta® (exenatide) injection, in 2005 by the FDA as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking
metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea but have not achieved adequate glycemic control. In 2005, Byetta
was the first GLP-1 product approved for use in the U.S. marketplace. Bydureon BCise (exenatide extended-release) injection
is a once-weekly administration and was approved for use in the U.S. in 2017.
In July 2023, we submitted an IND to support the initiation of clinical studies
with NPM-119. The proposed first-in-human study, called LIBERATE-1, was initially designed as a
12-week, randomized, clinical study to investigate the safety, tolerability, and full pharmacokinetic profile of NPM-119 in
patients with type 2 diabetes. In August 2023, FDA
provided written notification that the LIBERATE-1 study was on full clinical hold due primarily to insufficient CMC information. In June 2024, FDA lifted the clinical hold on the NPM-119 study and provided clearance to proceed with the originally designed LIBERATE-1 trials in patients with type 2 diabetes.
In parallel, Vivani decided to redesign the LIBERATE-1 study to support the NPM-115 program which resulted in changing the study population from type 2 diabetes patients to individuals with obesity and overweight. The main objectives of the goals of LIBERATE-1, namely, to study the safety, tolerability, and full pharmacokinetic profile of the exenatide implant, did not change. In addition to changing the LIBERATE-1 study population, the Company decided to conduct this newly designed LIBERATE-1 trial in Australia. On September 26, 2024, Vivani announced the receipt of regulatory approval to initiate the first-in-human, LIBERATE-1 clinical trial with a GLP-1 implant in obese and overweight individuals in Australia. Since clinical studies conducted in Australia comply with the International Conference on Harmonization
guidelines and data generated in Australia may be acceptable to the FDA and other regulatory authorities, Vivani plans to use
relevant clinical data generated in Australia to support regulatory submissions in other geographies including the United States.
Vivani
has also made progress towards preparing for future clinical development of NPM-119. In September 2023, Vivani relocated into
a new facility designed to provide suitable capacity for manufacturing of clinical materials for registration studies as well
as commercial-scale supply. Based on preliminary discussions with the FDA, Vivani intends to explore the potential use of the
505(b)(2) pathway and believes that a single pivotal trial evaluating a 6-month NPM-119 configuration that is representative of
the proposed commercial configuration may be sufficient to support registration in the United States. That said, as NPM-119
development proceeds, we intend to further engage with regulatory authorities on the timing, duration, endpoints, number of
enrolled patients and other aspects of trial design for future clinical trials of NPM-119.
We
have conducted a preclinical study to evaluate proof-of-concept activity of NPM-119. In that study, a six-month implantation of
NPM-119 into rats was associated with steady exenatide concentration over the duration of the implant, as depicted in the figure
below.
As depicted in the graph below, in a study in healthy rats, a single administration of the Company’s exenatide implant NPM-119, in development for the treatment of type 2 diabetes, resulted in body weights that were approximately 25% lower than a vehicle implant control after 15 weeks of treatment. NPM-119 delivered exenatide at a rate of approximately 320 nmol/kg/day and has demonstrated smooth, non-fluctuating release of exenatide in both in vitro and in vivo studies. NPM-119 has previously demonstrated pharmacokinetic data exhibiting continuous and therapeutic exenatide exposure levels over a 6-month duration in healthy rats. Since NPM-115 is a higher-dose version of an otherwise similar product as NPM-119, the durability of the effect on weight demonstrated in this study is expected to translate to future studies utilizing NPM-115.
OKV-119: Thisexenatideimplant is under development forcardiometabolicdiseases in companion cats, including the treatment of obesity and diabetes. In 2017, there were over 90 million cats in the U.S. It is estimated that up to 40% of cats are clinically obese, and 1-4 million cats have diabetes. Americans spent $136.8 billion on their pets in 2022, an increase of 10.68% from 2021. Spending on pets is expected to triple over the next 10 years, with pet health representing the fastest-growing sub-segment of this market. Since cats and dogs can be difficult to medicate, we believe that a small subdermal implant administered by a veterinarian at a routine clinic visit can be a welcome option for many pet owners, particularly those administrating daily insulin injections.
The program is partnered withOkavawho is responsible for all clinical development and regulatory activities of OKV-119 and, if approved, ultimate commercialization of this product. In 2022, OKV-119 advanced out of the feasibility stage after having produced data demonstrating adequateexenatideexposure and sustained weight loss in cats over a 12-week study.Vivanidoes not anticipate any significant focus or investment in this program beyond the support of implant development and manufacturing activities.
Beyond
our current pipeline, Vivani intends to apply its extensive experience and proprietary implant technology to develop a pipeline
of drug implant candidates that have the potential to address chronic diseases with high unmet medical needs across multiple therapeutic
categories and disease areas. For example, Vivani is also following the evaluation of the GLP-1 agonist semaglutide in the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”) and Alzheimer’s disease. If one or more of these trials shows encouraging
results, Vivani believes that a miniature long-term drug implant could have the potential to be an attractive alternative treatment
option in these underserved patient populations.
Our
Strategy
Vivani’s
mission is to provide people with the freedom to live healthier by revolutionizing the current treatment of chronic disease. Vivani develops miniaturized, ultra long-acting drug implants using its proprietary
NanoPortal implant technology to enable delivery of a broad range of medicines to treat chronic diseases. These products, designed
to address poor medication adherence, are anticipated to significantly improve the health of otherwise non-adherent patients and
to provide assurance to their family members and to the health care professionals who treat them that the medicine prescribed to them are taken as intended.
Vivani
plans to initially test its implant technology and business model through the clinical and regulatory development of its lead programs,
NPM-115 (high-dose exenatide implant) and NPM-139 (semaglutide implant). The active drugs, exenatide and semaglutide, are members of the GLP-1 receptor agonist
class of drugs. Drug products, including drug substances within this relatively new drug class, have already been successfully
developed and marketed for the treatment of both type 2 diabetes and obesity and GLP-1 products are the category leader in revenue
for both the type 2 diabetes and obesity/chronic weight management drug treatment categories. In addition, GLP-1 receptor agonists have shown promising
early clinical results in fatty liver disease or MASH, various addiction disorders, and other disease areas including Alzheimer’s disease. In 2024, Vivani has continued to execute its business strategy as evidenced by:
Competition
Our industry is characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. We face competition and potential competition from a number of sources, including pharmaceutical and biotechnology companies, generic drug companies, drug delivery companies and academic and research institutions. Some of these companies are developing therapies that are directly competitive to our approach. We believe the key competitive factors that will affect the development and commercial success of our product candidates include ease of administration and convenience of dosing, therapeutic efficacy, safety and tolerability profiles and cost. Many of our potential competitors have substantially greater financial, technical, and human resources than we do, as well as more experience in the development of product candidates, obtaining FDA and other foreign regulatory approvals of products, and the commercialization of those products. Consequently, our competitors may develop similar products to address the indications targeted by our current product candidates or for other indications we may pursue in the future, and such competitors’ products may be more effective, better tolerated and less costly than our product candidates. Our competitors may also be more successful in manufacturing and marketing their products than we are. We will also face competition in recruiting and retaining qualified personnel and establishing clinical trial sites and patient enrollment in clinical trials.
The
competition for Vivani will be dependent upon the individual product candidate in development. For Vivani’s lead programs,
NPM-115, NPM-139 and NPM-119, the competition could be defined as any drug product/manufacturer approved for use in the treatment of patients
with obesity or type 2 diabetes. However, we believe that our more direct competitors are restricted to other GLP-1 receptor
agonist and combination products with a GLP-1 receptor agonist component approved or in development for those respective indications.
In May 2022, Lilly’s Mounjaro® (tirzepatide) was approved as the first and only combination GIP and GLP-1 receptor
agonist for the treatment of adults with type 2 diabetes and in November 2023, Lilly secured approval of a higher dose formulation
of tirzepatide injection with the brand name Zepbound® for chronic weight management in adults with obesity or
overweight with at least one weight-related condition. Manufacturers with approved GLP-1 receptor agonists or dual receptor agonists
include Lilly, Novo Nordisk, AstraZeneca, and Sanofi.
The clinical adoption and commercial success of the GLP-1 class has been remarkable and already represents category leadership for obesity, weight management, sleep apnea in individuals with obesity, and type 2 diabetes medications from a revenue perspective. Vivani's product candidates, if approved, would compete in these large established markets. Obesity and overweight is a global epidemic. For example, over 1 billion adults and children currently live with obesity globally. The global prevalence of obesity has more than tripled since 1975. Today, less than 5% of these people are medically treated. Obesity affects both the individual and society at large. Obesity is associated with over 200 health complications and is associated with an increasing proportion of healthcare costs. According to the CDC, more than 37 million Americans have diabetes and 90-95% have type 2 diabetes. The total number of people living worldwide with diabetes today is 537 million and is projected to rise to 643 million by 2030 and 783 million by 2045. Of the 537 million people with diabetes today, only 15% have good glycemic control. According to the American Diabetes Association (“ADA”), the total cost of diagnosed diabetes in the U.S. was $327 billion in 2017, including $237 billion for direct medical costs and $90 billion for reduced productivity. In 2024, global sales of GLP-1 receptor agonists products (all indications) were over $50 billion and are projected to reach over $250 billion per year by 2034.
There are over 150 GLP-1 and dual and triple agonists and antagonists currently in clinical stage development for a wide variety of disorders including, but not limited to, obesity, chronic weight management, chronic sleep apnea associated with obesity, kidney disease, certain neurological disorders, and various addiction disorders. The listing below, while not comprehensive, provides a representative sampling of GLP-1 compounds in clinical-stage development for obesity, chronic weight management, and/or type 2 diabetes and are considered future potential competitors to Vivani's emerging portfolio of miniature, ultra long-acting GLP-1 drug implants.
● Altimmune's pemvidutide (ALT 801)
● Amgen's MariTide (maridebart cafraglutide, formerly AMG 133)
● AstraZeneca and Eccogene's ECC5004
● D&D Pharmatech's DD01
● Fractyl Health's Rejuva (GLP-1 based pancreatic gene therapy)
● Lilly's retatrutide; orforglipron;
● Lilly and Innovent's mazdutide (LY3305677)
● Merck's efinopeglutide
● Novo Nordisk CagriSema
● Pfizer's danuglipron
● Structure Therapeutic's GSBR 1290
● Tern Pharmaceutical's TERN-601
● Viking Therapuetic's VK 2735
● Zealand Pharma's dapiglutide
● Zealand Pharma and Boehringer Ingelheim's survodutide (BI 456906)
NPM-115 and NPM-139
NPM-115 is a miniature, six-month, (high-dose) exenatide implant candidate in development for the treatment of chronic weight management
in individuals with obesity or overweight. NPM-139 (semaglutide implant) candidate, the same GLP-1 active pharmaceutical ingredient as Ozempic and Wegovy, is also in development for the treatment of chronic weight management in obese and/or overweight patients. NPM-139 has the added potential benefit of once-yearly dosing.
A listing of products currently approved in the US for the treatment of obesity and/or chronic weight management are provided below:
● Teva’s Adipex® (phentermine) and generics
● Roche’s Xenical® (orlistat) and generics
● Vivus’s Qsymia® (phentermine/topiramate extended release)
● Orexigen’s Contrave® (bupropion/naltrexone)
● Lilly (Zepbound®/tirzepatide)
● Novo Nordisk (Saxenda®/liraglutide); and (Wegovy/semaglutide)
A listing of GLP-1 monotherapy agonists, dual agonists and triple agonists
in various stages of clinical development is provided in the preceding section. We believe NPM-115, our lead drug implant candidate for chronic weight management, has the potential to address two important aspects of the GLP-1 category which are associated with the above-mentioned products, namely, poor real-world medication adherence and potential undesirable gastrointestinal tolerability.
NPM-119
NPM-119
(exenatide implant) candidate is a GLP-1 receptor agonist in development for the treatment of type 2 diabetes. Competition in
the GLP-1 class for this indication includes the following:
● Lilly (Trulicity®/dulaglutide) and (Mounjaro®/ tirzepatide)
● AstraZeneca (Bydureon BCise®/exenatide); and (Byetta/exenatide)
● Sanofi (Adlyxin®/lixisenatide)
A listing of GLP-1 monotherapy agonists, dual agonists and triple agonists in various stages of clinical development is provided in the preceding section. We believe NPM-115, our lead drug implant candidate for chronic weight management, has the potential to address two important aspects of the GLP-1 category which are associated with the above-mentioned products, namely, poor real-world medication adherence and potential undesirable gastrointestinal tolerability.
Sales and Marketing
Vivanicurrently does not have a commercial infrastructure in any geography. As we progress our programs through development, we plan to build a commercial infrastructure in the United States or selected other territories to support the commercialization of each of our product candidates when we believe a regulatory approval in a particular territory is likely. We intend to conduct market research in connection with designing our commercialization strategy for each of our product candidates. We may seek licensing or other strategic collaborations with, for example, global pharmaceutical company partners, to support our commercialization efforts. We will consider a range of options including building a commercial capability internally, leveraging third-partybiopharmaceuticalcommercialization organizations, other strategic partners, distributors and/or contract sales forces to expand the commercial availability of our product candidates when appropriate.
Our Corporate Information
Vivani(as Second Sight Medical Products)was incorporatedon December 17, 2009under the laws of the State of California. Its operations began in 2010. After the successful merger of Second Sight Medical Products andNanoPrecisionMedical on August 30, 2022, the combined company was renamedVivaniMedical,Inc. Prior to the merger,NanoPrecisionMedical was a private company.
On July 6, 2023,Vivanichanged its state of incorporation from the State of California to the State of Delaware by means of a plan of conversion, effective July 5, 2023.
Vivani’scorporate office is located at 1350 South Loop Road, Alameda, CA 94502; its telephone number is (415) 506-8462; and its website is located at www.vivani.com.
Chemistry,
Manufacturing, and Controls
Vivani
has developed production processes and quality systems to support the manufacture of clinical materials for its emerging portfolio of miniature, ultra long-acting GLP-1 drug implants. For example, Vivani recently initiated LIBERATE-1, a Phase 1 study of an exenatide implant in individuals who have obesity or overweight at two clinical study sites in Australia to support the NPM-115 program.
Vivani has established in-house
research, development, and manufacturing capabilities in its corporate headquarters in Alameda, California, U.S. Vivani has
also engaged with contract manufacturers and analytical laboratories for selected processes when appropriate. In general,
Vivani purchases the drug substance from a third-party manufacturer. Vivani intends to conduct all assembly processes in
which the drug substance is present, including the associated in-process testing, when producing materials for Phase 1 and
Phase 2 clinical trials. Vivani anticipates that all assembly processes in which the drug substance is present, including the
associated in-process testing, will be performed either in-house or by contract manufacturers when producing materials for any registration
trial or commercial use. Several device components and all raw materials are purchased from outside vendors according to
established specifications. The device assembly processes, including the associated in-process testing, and final product
testing are anticipated to be performed by Vivani in Alameda, California. The custom applicator, which is intended to
facilitate subdermal placement of the implant in patients, has been designed and will be manufactured by a contract
manufacturer. Several device components and the drug substance are purchased from outside vendors according to established
specifications.
As our portfolio of drug implant candidates advances, Vivani may also engage additional contract analytical and manufacturing organizations as needed.
Currently, Vivani is not a party to any long-term, commercial manufacturing agreements.
Intellectual Property
As ofDecember 31, 2024,Vivaniheld or controlled 16 issued U.S. patents, 10 pending U.S. patent applications, and 7 patents in various jurisdictions outside the United States. Additionally,Vivaniis pursuing 24 corresponding patent applications that are pending in various foreign jurisdictions, and 4 international patent applications. Further advancement ofVivani’sintellectual property portfolio will require the filing of patent applications related to its proprietary manufacturing process and product candidates.Vivanihas patents extending into China, Hong Kong, India, Japan, Republic of Korea, and the United States of America, as well as trade secrets protectingVivani’sintellectual property.Vivani’spatent prosecution strategy includes exploration of opportunities to expand its patent life and use cases in order to broaden its existing patent portfolio.
Below is a further description of certain ofVivani’skey issued patents, including the category of protection, expiration date, number of related patents issued in foreign jurisdictions and the product candidates to which each patent relates.Vivanicurrently holds or controls:
Wherever
possible, Vivani seeks to protect its inventions by filing U.S. patents as well as foreign counterpart applications in select
other countries. Because patent applications in the U.S. are maintained in secrecy for at least eighteen months after the applications
are filed, and since publication of discoveries in the scientific or patent literature often lags behind actual discoveries, Vivani
cannot be certain that it was the first to make the inventions covered by each of its issued or pending patent applications, or
that Vivani was the first to file for protection of inventions set forth in such patent applications. Vivani’s planned,
or potential products may be covered by third-party patents or other intellectual property rights, in which case continued development
and marketing of its products would require a license. Required licenses may not be available to Vivani on commercially acceptable
terms, if at all. If Vivani does not obtain these licenses, it could encounter delays in product introductions while it attempts
to design around the patents, or Vivani could find that the development, manufacture, or sale of products requiring such licenses
are not possible.
In
addition to patent protection, Vivani also relies on know-how, trade secrets, and the careful monitoring of proprietary information,
all of which can be difficult to protect. Vivani seeks to protect some of its proprietary technology and processes by entering
into confidentiality agreements with its employees, consultants, and contractors. These agreements may be breached, Vivani may
not have adequate remedies for any breach and its trade secrets may otherwise become known or be independently discovered by competitors.
To the extent that Vivani’s employees or its consultants or contractors use intellectual property owned by others in their
work for Vivani, disputes may also arise as to the rights in related or resulting know-how and inventions.
Government Regulation
Regulatory authorities in the U.S. at the federal, state, and local level and in other countries extensively regulate, among other things, the research and clinical development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing, pricing, and export and import of drugs, medical devices and combinations of drugs and devices (combination products) such as those we are developing. Generally, before a new drug or drug-device combination product can be marketed, considerable data demonstrating its quality, safety, and efficacy must be obtained, organized into a format specific to each regulatory authority, submitted for review, and approved by the relevant regulatory authority.
In
the U.S., the FDA regulates drugs, devices and combination products under the Federal Food, Drug, and Cosmetic Act (“FDCA”),
and its implementing regulations. These products are also subject to other federal, state and local statutes and regulations.
The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign
statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with the applicable
U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant
to administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s, or another regulatory
authority’s, refusal to approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters,
product recalls or withdrawals from the market, product seizures, total or partial suspension of production or distribution, injunctions,
fines, debarment, refusals of government contracts, restitution, disgorgement, or civil or criminal penalties. Any agency or judicial
enforcement action could have a material adverse effect on us.
U.S.
Drug Development
Our
product candidates are subject to regulation as combination products, which means that they are composed of both a drug product
and device product. If marketed individually, each component would be subject to different regulatory pathways and reviewed by
different centers within the FDA. A combination product, however, is assigned to a center that will have primary jurisdiction
over its regulation based on a determination of the combination product’s primary mode of action, which is the single mode
of action that provides the most important therapeutic action. In the case of our product candidates, the primary mode of action
is attributable to the drug component of the product, which means that the FDA’s Center for Drug Evaluation and Research
has primary jurisdiction over the premarket development, review and approval of our product candidates. Accordingly, we plan to
investigate our products through the IND framework and seek approval through the NDA pathway. The process required by the FDA
before a drug may be marketed in the U.S. generally involves the following:
● payment of associated user fees;
● review by an FDA advisory committee, where appropriate or if applicable;
Once a pharmaceutical product candidate is identified for development, it enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity, formulation and stability, as well as animal studies. A sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature, to the FDA as part of the IND. An IND is an exemption from the FDCA that allows an unapproved product to be shipped in interstate commerce for use in an investigational clinical trial and a request for FDA authorization to administer such investigational product to humans. The sponsor must also include a protocol detailing, among other things, the objectives of the initial clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated if the initial clinical trial lends itself to an efficacy evaluation. Some preclinical testing may continue after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions related to a proposed clinical trial and places the trial on a clinical hold within that 30-day period. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns or non-compliance and may be imposed on all drug products within a certain class of drugs. The FDA also can impose partial clinical holds, for example, prohibiting the initiation of clinical trials of a certain duration or for a certain dose.
All
clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCP regulations.
These regulations include the requirement that all research subjects provide informed consent in writing before their participation
in any clinical trial. Further, an IRB must review and approve the plan for any clinical trial before it commences at any institution,
and the IRB must conduct continuing review and reapprove the study at least annually. An IRB considers, among other things, whether
the risks to individuals participating in the clinical trial are minimized and are reasonable in relation to anticipated benefits.
The IRB also approves the information regarding the clinical trial and the consent form that must be provided to each clinical
trial subject or his or her legal representative and must monitor the clinical trial until completed.
Each
new clinical protocol and any amendments to the protocol must be submitted for FDA review, and to the IRBs for approval. Protocols
detail, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria,
and the parameters to be used to monitor subject safety.
Human
clinical trials are typically conducted in three sequential phases that may overlap or be combined:
Post-approval
trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These studies are
used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances,
the FDA may mandate the performance of Phase 4 trials. Companies also are required to register certain clinical trials and post the results of those clinical trials on a government-sponsored database, such as ClinicalTrials.gov in the United
States, within certain timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.
Progress
reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA,
and written IND safety reports must be submitted on an expedited basis to the FDA and the investigators for serious and unexpected adverse events, findings
from other studies that suggest a significant risk to humans exposed to the product, findings from animal or in vitro testing
that suggest a significant risk to human subjects, and any clinically important increase in the rate of a serious suspected adverse
reaction over that listed in the protocol or investigator brochure. The FDA or the clinical trial sponsor may suspend or terminate a clinical
trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable
health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial
is not being conducted in accordance with the IRB’s requirements or if the product has been associated with unexpected serious
harm to patients. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the
clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether a
trial may move forward at designated check points based on access to certain data from the study. The clinical trial sponsor may
also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.
Concurrent
with clinical trials, companies usually complete additional animal studies and must also develop additional information about
the chemistry and physical characteristics of the product and finalize a process for manufacturing the product in commercial quantities
in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the
product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and
purity of the final product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted
to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life. In addition, for certain
combination products it may be necessary to conduct human factors studies prior to NDA submission to ascertain the usability of
the product by patients in real-world settings.
NDA and FDA Review Process
The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the drug, proposed labeling and other relevant information, are submitted to the FDA as part of an NDA for a new drug, requesting approval to market the product. An NDA for a new drug must contain proof of the drug’s safety and efficacy. The submission of an NDA is subject to the payment of a substantial application user fee, and the sponsor of an approved NDA is also subject to an annual program user fee, although waivers of some fees may be obtained under certain limited circumstances. For example, the agency will waive the application fee for the first human drug application that a small business or its affiliate submits for review.
The
FDA reviews all NDAs submitted before it accepts them for filing and may request additional information rather than accepting
an NDA for filing. The FDA typically makes a decision on accepting an NDA for filing within 60 days of receipt. The decision to
accept the NDA for filing means that the FDA has made a threshold determination that the application is sufficiently complete
to permit a substantive review. Under the goals and policies agreed to by the FDA under the Prescription Drug User Fee Act (PDUFA),
the FDA’s goal to complete its substantive review of a standard NDA and respond to the applicant is ten months from the filing of the NDA. The FDA does not always meet its PDUFA goal dates, and the review process is often significantly extended
by FDA requests for additional information or clarification and may go through multiple review cycles.
After
the NDA submission is accepted for filing, the FDA reviews the NDA to determine, among other things, whether the proposed product
is safe and effective for its intended use, and whether the product is being manufactured in accordance with cGMPs to assure and
preserve the product’s identity, strength, quality and purity. During its review, the FDA will likely re-analyze the clinical
trial data, which could result in extensive discussions between the FDA and us during the review process. The review and evaluation
of an NDA by the FDA is extensive and time consuming and may take longer than originally planned to complete, and we may not receive
a timely approval, if at all. The FDA may refer applications for novel drug products or drug products which present difficult
questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review,
evaluation and a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound
by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.
Before
approving an NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine
whether they comply with cGMPs. The FDA will not approve the product unless it determines that the manufacturing processes and
facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required
specifications. In reviewing the NDA for a drug-device combination product, FDA reviewers in the drug center will consult with
their counterparts in the device center to ensure that the device component of the combination product meets applicable requirements
regarding safety, effectiveness, durability and performance. Under FDA regulations, combination products are subject
to cGMP requirements applicable to both drugs and devices, including the Quality System Regulations (“QSRs”) applicable
to medical devices. In addition, before approving an NDA, the FDA may inspect certain clinical trial sites and audit data from clinical trials to ensure compliance
with GCP requirements. After the FDA evaluates the application, manufacturing process and manufacturing facilities, it may issue