UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
☒ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2024
OR
☐TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from ______________ to
______________
Commission File Number: 001-39138
JASPER THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
(Address of principal executive offices) (Zip Code)
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
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 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 every Interactive Data File required to be submitted 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, a smaller reporting company, or an emerging growth company.
See the definitions 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 voting and non-voting common equity
held by non-affiliates of the registrant as of June 30, 2024 (the last business day of the registrant’s most recently completed
second fiscal quarter) was approximately $281.0 million based on the closing price of the registrant’s common stock on June 30,
2024 of $22.70 per share, as reported by the Nasdaq Capital Market.
As of February 25, 2025, the number of shares of
the registrant’s common stock outstanding was 15,022,122 shares of voting common stock, $0.0001 par value per share, and no shares
of non-voting common stock, $0.0001 par value per share.
DOCUMENTS INCORPORATED BY REFERENCE
None.
TABLE OF CONTENTS
PART I
Item 1. Business 1
Item 1A. Risk Factors 23
Item 1B. Unresolved Staff Comments 83
Item 1C. Cybersecurity 83
Item 2. Properties 84
Item 3. Legal Proceedings 84
Item 4. Mine Safety Disclosures 84
PART II
Item 6. [Reserved] 85
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 99
Item 8. Financial Statements and Supplementary Data F-1
Item 9A. Controls and Procedures 100
Item 9B. Other Information 100
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 100
PART III
Item 10. Directors, Executive Officers and Corporate Governance 101
Item 11. Executive Compensation 114
PART IV
Item 14. Principal Accountant Fees and Services 130
Item 15. Exhibit and Financial Statement Schedules 131
i
JASPER THERAPEUTICS, INC.
As used in this Annual Report on Form 10-K, unless
the context requires otherwise, references to the “Company”, “Jasper”, “we”, “us”, “our”,
and similar terms refer to Jasper Therapeutics, Inc., a Delaware corporation formerly known as Amplitude Healthcare Acquisition Corporation
(“AMHC”), and its consolidated subsidiary. References to “Old Jasper” refer to the private Delaware corporation
that is now our wholly-owned subsidiary and named Jasper Tx Corp. (formerly known as Jasper Therapeutics, Inc.).
On September 24, 2021, we consummated the
previously announced Business Combination (as defined below) (pursuant to the Business Combination Agreement, dated May 5, 2021, by
and among AMHC, Ample Merger Sub, Inc. (“Merger Sub”) and Old Jasper). Pursuant to the terms of the Business Combination
Agreement, a business combination (herein referred to as the “Business Combination” or “Reverse
Recapitalization” for accounting purposes) between AMHC and Old Jasper was effected through the merger of Merger Sub with and
into Old Jasper with Old Jasper surviving as AMHC’s wholly-owned subsidiary. In connection with the Business Combination, AMHC
changed its name from Amplitude Healthcare Acquisition Corporation to Jasper Therapeutics, Inc.
Unless otherwise noted or the context requires
otherwise, references to our “common stock” refer to our voting common stock, par value $0.0001 per share. In addition, except
as otherwise indicated, all information in this Annual Report on Form 10-K gives effect to the 1-for-10 reverse stock split of the common
stock that was effected on January 4, 2024.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
Certain statements contained in this Annual Report
on Form 10-K may constitute “forward-looking statements” for purposes of federal securities laws. Such statements can be identified
by the fact that they do not relate strictly to historical or current facts. In addition, any statements that refer to projections, forecasts
or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The
words “anticipate,” “believe,” “contemplate,” “continue,”
“could,” “estimate,” “expect,” “intends,” “may,”
“might,” “plan,” “possible,” “potential,” “predict,”
“project,” “should,” “will,” “would” and similar expressions
(including the negative of any of the foregoing) may identify forward-looking statements, but the absence of these words does not mean
that a statement is not forward-looking.
Forward-looking statements in this Annual Report
on Form 10-K may include, for example, but are not limited to, statements about:
● our ability to research, discover and develop additional product candidates;
● the potential attributes and benefits of our product candidates;
● our ability to obtain funding for our operations;
● our public securities’ potential liquidity and trading;
ii
● our ability to grow and manage growth profitably;
● our ability to identify, in-license or acquire additional technology; and
These forward-looking statements are based on current
expectations and beliefs concerning future developments and their potential effects. There can be no assurance that future developments
affecting us will be those that we have anticipated. These forward-looking statements involve a number of risks, uncertainties (some of
which are beyond our control) or other assumptions that may cause actual results or performance to be materially different from those
expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to, those factors
described under the heading “Risk Factors” in this Annual Report on Form 10-K. Should one or more of these risks or uncertainties
materialize, or should any of our assumptions prove incorrect, actual results may vary in material respects from those projected in these
forward-looking statements. There may be additional risks that we consider immaterial or which are unknown. It is not possible to predict
or identify all such risks. Readers are cautioned not to place undue reliance on forward-looking statements because of the risks and uncertainties
related to them and to the risk factors. We do not undertake any obligation to update or revise any forward-looking statements, whether
as a result of new information, future events or otherwise, except as may be required under applicable securities laws.
iii
PART I
ITEM 1. BUSINESS
Overview
We are a clinical-stage biotechnology company
focused on developing therapeutics targeting mast cell driven diseases such as Chronic Spontaneous Urticaria (“CSU”), Chronic
Inducible Urticaria (“CIndU”) and Asthma. We are evaluating additional indications in mast cell driven diseases for potential
future development and we have also historically supported development programs in diseases where targeting diseased hemopoietic stem
cells can provide benefits, such as and stem cell transplant conditioning regimens.
Our
lead product candidate, briquilimab, is a monoclonal antibody designed to block stem cell factor (“SCF”) from binding to
and signaling through the CD117 (“c-Kit”) receptor on mast and stem cells. The SCF/c-Kit pathway is a survival signal for
mast cells and we believe that blocking this pathway may lead to depletion of these cells throughout the body, including in the lungs
and in the skin, which could lead to significant clinical benefit for patients with mast-cell driven diseases such as asthma and chronic
urticarias. To that end, we are focusing on advancing a portfolio of clinical programs in mast cell driven diseases. Development highlights
include:
○ Briquilimab demonstrated a rapid onset of clinical efficacy:
● Clinical responses were seen as early as 1 week post-dose; and
● Complete responses were observed as early as week 2 post-dose
○ Briquilimab drove deep and meaningful clinical responses:
● Complete responses showed durability out to:
○ Briquilimab was well tolerated and demonstrated a favorable safety profile:
● We commenced a Phase 1b/2a ETESIAN study in Asthma in late 2024.
1
We
are also developing briquilimab as a one-time conditioning therapy for severe combined immunodeficiency (“SCID”) patients
undergoing a second stem cell transplant for which we are currently conducting a Phase 1/2 clinical trial.
We intend to become a fully integrated discovery,
development and commercial company in the field of mast cell therapeutics. We are developing our product candidates to be used individually
or, in some cases, in combination with other therapeutics. Our goal is to advance our product candidates through regulatory approval and
bring them to the commercial market based on the data from our clinical trials and communications with regulatory agencies and payor communities.
We expect to continue to broaden our pipeline with additional mast cell indications and next-generation products by leveraging our research
organization.
We have an exclusive license agreement with Amgen Inc. (“Amgen”)
for the development and commercialization of the briquilimab monoclonal antibody in all indications and territories worldwide. We also
have an exclusive license agreement with Stanford for the right to use briquilimab in the clearance of diseased stem cells prior to the
transplantation of hematopoietic stem cells (“HSCs”).
Briquilimab
We believe briquilimab is a unique, humanized,
monoclonal antibody that targets the underlying biology of mast cell survival to potentially serve as a therapeutic to prevent mast cell
driven diseases. In addition, we believe briquilimab targets a key differentiation pathway for HSCs and may be developed to improve the
efficacy and safety of hematopoietic stem cell transplantation. Briquilimab binds to human c-Kit, the receptor for SCF, which is expressed
on the surface of various cells, including mast cells and hematopoietic stem and progenitor cells. The interaction of SCF and c-Kit is
required for mast cells to survive and for HSCs to remain in the bone marrow. By blocking SCF from binding to c-Kit and disrupting these
critical signals, briquilimab leads to the depletion of mast cells in the skin and the differentiation of stem cells in the bone marrow.
Briquilimab is designed to bind to c-Kit with a greater affinity than SCF.
The monoclonal antibody isotype and other modifications
of briquilimab were chosen carefully to retain high affinity binding to the c-Kit receptor and SCF signal blockade without recruiting
other immune cells that could lead to receptor activation, mast cell degranulation or other off-target toxicities. For example, designing
briquilimab as an IgG1 isotype instead of an IgG2 isotype results in more potent inhibition of c-Kit, potentially increasing the effect
on mast cell depletion. Briquilimab was also designed to be aglycosylated in order to eliminate the recruitment of other immune effector
cells that may bring unwanted effects to any cell that expresses c-Kit. This finding and other data demonstrate that not all anti-c-Kit
antibodies behave equally or have the same mechanism of action.
We are focused on advancing Briquilimab in development
as a chronic therapy in mast cell driven diseases such as CSU, CIndU, Asthma and other mast cell driven indications currently under evaluation.
We also currently have an ongoing study evaluating Briquilimab as a conditioning agent to clear HSCs from the bone marrow prior to re-transplant
in patients with SCID.
Briquilimab as a Primary Therapeutic for Disorders
of Mast Cells
Mast cells are primary cells of the immune system
derived from HSCs in the bone marrow. Mast cells store a number of different chemical mediators such as tryptase, histamine, interleukins
and heparin in granules found throughout the cell. When a mast cell is triggered, such as by an allergen specific to membrane-bound Immunoglobulin
E (“IgE”) antibodies, the mast cell is activated and releases the content of the granules into the surrounding tissue. These
chemical mediators attract other immune cells to help with any response as well as produce a local allergic reaction consisting of inflammation,
swelling, contraction of smooth muscle and increased mucus secretion. Mast cells are usually long-lived and found at boundaries to the
external environment such as the skin, mucosal surfaces of the gut and lungs and eye.
Dysfunctional regulation and activation of mast
cells is thought to be a significant driver of multiple diseases, including urticarias, asthma, prurigo nodularis, allergic eye disease
and others. Each of these diseases has been shown to have local concentrations of mast cells, cellular response consistent with mast cell
degranulation and disease modification with use of antihistamines. Unfortunately, currently approved agents targeting mast cells in these
diseases are ineffective in many patients, leading to continued high disease burden.
2
Briquilimab blocks signaling on the c-Kit receptor
by inhibiting the binding of SCF, the ligand for the c-Kit receptor. The interaction of SCF/c-Kit on mast cells is critical for development,
proliferation and survival. Without continued signaling through c-Kit, mast cells will undergo apoptosis and die. We have shown that a
single subcutaneous dose of briquilimab leads to depletion of mast cells in the skin of healthy human volunteers for at least 29 days.
We believe that depletion of mast cells in the skin of patients with chronic urticaria or other mast cell driven diseases has the potential
to lead to improved disease control for those patients without adequate response to current therapies.
Figure 1 – Healthy volunteers administered single
doses of briquilimab 42 mg to 280 mg subcutaneously received punch skin biopsies to evaluate the decreases in mast cells at 4 weeks after
briquilimab was administered compared to the baseline.
(1) Jasper internal data (Phase 1a, healthy volunteer study).
Briquilimab in Chronic Urticaria
Mast cells are immune cells that play a key role
in the inflammatory response to pathogens or injury and are typically found in the skin, lungs, digestive track, conjunctiva of the eye
and the mucosal linings of the mouth and nose. Typically, mast cells are triggered by a specific antigen or antibody interaction to release
histamine, a variety of cytokines and other chemical mediators in order fight a potential infection and to recruit additional types of
immune cells to aid in the body’s response. However, with certain diseases, such as CSU, CIndU, allergic asthma, prurigo nodularis
and eosinophilic esophagitis, the mast cell response is dysregulated and may lead to unwanted responses such as hives, itching, airway
constriction or conjunctivitis. Current therapeutic approaches to controlling mast cell response include antihistamines to counteract
the release of histamine by activated mast cells and anti-IgE antibody therapy to try to eliminate the antibodies responsible for a trigger
of mast cell activation. We believe that new chronic therapies that target mast cells could be beneficial in treating many diseases that
are a function of mast cell dysfunction.
3
In late 2023, we commenced a Phase 1b/2a clinical study in patients
with CSU. CSU is a disorder of mast cells in the skin in which patients experience swelling, redness and itching of the skin that lasts
at least six weeks due to either an unknown cause, Type I autoimmunity with Immunoglobulin E antibodies (“IgE”) against self
or Type IIb autoimmunity with activating antibodies directed at mast cells. CSU is thought to affect over five million patients in the
United States, France, Germany, Italy, Spain, and the United Kingdom. The U.S. Food and Drug Administration (the “FDA”)-approved
drug therapy for CSU includes second generation H1-antihistamines for first line use followed by consideration for use of omalizumab,
a monoclonal antibody directed at circulating IgE. The biologic rationale for both of these therapies is based on modulating mast cell
response. Antihistamines work to counteract the effects of histamine that is released from activated mast cells and omalizumab is designed
to reduce IgE, which is thought to be a trigger of mast cell activation. Based on human healthy volunteer clinical data showing that briquilimab
can deplete mast cells from the skin and from data in a study of CSU patients showing that an anti-c-Kit antibody can control disease
symptoms, we believe that briquilimab could be effective therapy for CSU patients. The Phase 1b/2a study is a monotherapy study being
conducted in CSU patients who are refractory to antihistamine therapy and who have had an inadequate response to omalizumab. The study
design has three parts. The first part is an open-label 3+3 dose escalation with two dose cohorts (10mg and 40mg). The second part consists
of seven dose cohorts (80mg Q8W, 120mg Q8W, 120mg Q12W, 180mg Q8W, 180mg Q12W, 240mg Q8W and 240mg followed by 180mg Q8W) in a double-blind
placebo controlled format. The final part is a single dose cohort with two dose levels being explored (240mg single-dose and 360mg single-dose)
in a double-blind placebo controlled format.
Figure 3 – Study Design for the Phase
1b/2a CSU Study
We commenced the Phase 1b/2a BEACON study in CSU in late 2023. In
January 2025, we presented positive preliminary data from the first 8 dosing cohorts in the study (10mg, 40mg, 80mg Q8W, 120mg Q8W, 120mg
Q12W, 180mg Q8W, 180mg Q12W, 240mg single-dose). Patient duration
on study as of the cutoff date for the data presented was as long as 28 weeks:
o Briquilimab demonstrated a rapid onset of deep clinical responses
● UAS7 reductions with much as 29 points noted 4 weeks post-dose (120mg Q12W)
● 100% complete responses through 8 weeks demonstrated at the 240mg dose level
4
o Briquilimab was well-tolerated and demonstrated a favorable safety profile
● C-kit related AEs were low frequency, transient, low-grade events
● C-kit related AEs were low frequency, transient, low-grade events
● The majority of AEs observed resolved while on study prior to subsequent doses
We are also conducting a Phase 1b/2a clinical study
in patients with CIndU. Similar to CSU, CIndU is a disorder of mast cells in the skin in which patients experience swelling, redness and
itching of the skin that lasts at least six weeks, but CIndU is induced by specific physical or environmental stimuli, including cold,
heat, exercise, pressure, sunlight and others. CIndU includes physical urticarias, such as symptomatic dermographism and cold urticaria,
as well as non-physical urticarias caused by exposure to specific stimuli, such as cholinergic urticaria and aquagenic urticaria.
The FDA-approved drug therapy for CIndU consists
solely of second generation H1-antihistamines. The biologic rationale for this therapy is based on modulating mast cell response. Antihistamines
work to counteract the effects of histamine that is released from activated mast cells. CIndU is thought to affect over two million patients
in the United States, France, Germany, Italy, Spain and the United Kingdom. Approximately 40% of these patients’ CIndU is not controlled
by first line antihistamines and these patients could be eligible for biologic therapy depending on disease severity. Based on preclinical
and human healthy volunteer clinical data showing that briquilimab can deplete mast cells from the skin, we believe that briquilimab could
be an effective therapeutic for CIndU patients. The Phase 1b/2a study is a monotherapy study being conducted in CIndU patients who are
refractory to antihistamine therapy. The study design contains a single dose in three dosing cohorts (40mg, 120mg and 180mg) with a provocation
test measured at 12 weeks post-dosing.
Figure 4 – Study Design for the Phase
1b/2a CIndU Study
5
We commenced the Phase 1b/2a SPOTLIGHT study in CIndU in early 2024.
In October 2024, we presented positive preliminary data on the 40mg and 120mg cohorts from the study showing the following for the 6-week
preliminary analysis period following dosing:
Briquilimab in Asthma
Allergic asthma is a form of asthma triggered by
specific allergens that leads to constriction of smooth muscles in the airways, cellular infiltration of various immune mediators and
excess production of mucus. Patients with allergic asthma may have an increased number of mast cells in the bronchi and mast cells are
believed to not only be a direct driver of inflammation the asthmatic response, but to also be recruiters of other cell types that contribute
to that inflammation. Given these factors, we believe that asthma may be responsive to agents that modulate mast cell response, including
antihistamines and anti-IgE monoclonal antibody therapy.
In late 2024, we commenced a Phase 1b/2a clinical
study in patients with allergic asthma. The Phase 1b/2a study is a double-blind placebo controlled single-dose monotherapy allergen challenge
study being conducted in allergic asthma patients. Patients enrolled in the study will either receive placebo, or a single 180mg dose
of briquilimab. Endpoints evaluated will include both asthmatic response, as measured by % decrease in FEV1 relative to baseline, and
change in airway hyperresponsiveness from baseline, and both will be measured at 6 weeks post-dose and 12 weeks post-dose.
Figure 5 – Study Design for the Phase
1b/2a Asthma Study
Briquilimab in Other Mast Cell Disorders
Mast cells may also be the key cellular target for a number of other
inflammatory or autoimmune diseases outside of the chronic urticarias and asthma, such as atopic dermatitis, eosinophilic esophagitis
or prurigo nodularis.
Atopic dermatitis is a chronic disease that causes
inflammation, redness, and irritation of the skin. It is a common condition that usually begins in childhood; however, anyone can get
the disease at any age. Atopic dermatitis causes the skin to become extremely itchy. In most cases, there are periods of time when the
disease is worse, called flares, followed by periods when the skin improves or clears up entirely, called remissions. Treatments include
moisturizers, topical steroids, immunomodulators (tacrolimus and pimecrolimus) and biologic therapies (dupilumab). Mast cells may
play an important role in the disease and agents that modulate mast cells may provide benefit to patients.
Eosinophilic esophagitis is an immune disorder
leading to build up of eosinophils in the esophagus and causes difficulty in eating, chronic reflux and/or the sensation of heartburn.
Along with the buildup of eosinophils, there is typically buildup of other immune cells in the affected area including mast cells, basophils
and lymphocytes. Patients may be treated with changes to diet, use of proton pump inhibitors, antihistamines and dupilumab.
Prurigo Nodularis is also a disease that
manifests in the skin. Patients develop severe itch and firm bumps on the skin, called nodules, that may lead to loss of sleep and
bleeding due to scratching. Degranulation of mast cells in the skin is thought to trigger peripheral sensory neurons in the skin
leading to itch. Various medications are used to treat Prurigo Nodularis including anti-itch creams and topical steroids. For cases
that remain uncontrolled physicians may prescribe antihistamines or biologics such as dupilumab.
We are currently engaged in pre-clinical evaluation
of briquilimab as a potential therapeutic in these and a number of other mast cell driven diseases and expect to continue to expand our
portfolio of mast cell indications in clinical development moving forward.
6
Briquilimab as a Conditioning Agent for SCID Patients Undergoing
Re-Transplantation
We are also developing briquilimab as a conditioning
agent for SCID patients undergoing a stem cell re-transplantation. Due to genetic errors at birth, SCID patients do not possess fully
functional immune systems, which results in chronic infections, failure to thrive and significantly decreased lifespans. If available,
these patients are typically given a transplant from a close relative with the goal of allowing healthy donor stem cells to establish
in the patient’s bone marrow, leading to production of normal immune cells. However, stem cell transplants are not universally successful.
SCID patients with poor transplant outcomes are typically dependent on external therapies such as intravenous immunoglobin (“IVIG”)
and often have poor immunity, leading to chronic infections and decreased lifespans. SCID patients who fail transplant are not usually
given a second transplant due to their fragile health and the significant toxicities of current conditioning agents.
SCID is a genetically heterogeneous group of over 20 monogenic conditions
of the immune system characterized by the lack of normal T lymphocyte development, in addition to deficiencies of B cells, NK cells, or
both in some forms which is currently curable only by hematopoietic cell transplant (“HCT”). The incidence of SCID is estimated
at one in 80,000 live births across all ethnic groups. Due to the toxicities associated with the current chemotherapy regimens used in
standard allogeneic HCT to deplete endogenous HSC, some centers do not use conditioning regimens. SCID patients who undergo unconditioned
HCT have relatively improved overall survival but often experience incomplete immune reconstitution characterized by inadequate T cell
numbers and/or ongoing deficiency of B cell humoral immunity. This issue occurs more frequently in those patients who do not have a human
leukocyte antigen-matched donor and who therefore receive T cell depleted haploidentical donor grafts.
Patients who receive full or reduced doses of busulfan
conditioning (a DNA damaging drug) tend to engraft well and have full lymphocyte reconstitution. However, due to busulfan’s off-target
toxic effects, these patients experience both short- and long-term complications. Since these patients typically receive busulfan as infants,
they experience chronic complications such as growth retardation, cognitive defects, craniofacial abnormalities, liver toxicity, seizures
and endocrine defects, including infertility, and increased cancer risk.
Pre-clinical Data for Briquilimab for Severe Combined Immunodeficiency
Re-Transplantation
The ability of briquilimab to open a human hematopoietic
stem cell niche was evaluated in humanized immune deficient mice that were stably engrafted with human hematopoietic grafts at Stanford.
Two weeks after a single treatment with 0.3 mg/kg or 1.0 mg/kg of briquilimab, mice showed depletion of human HSCs and progenitor cells
(CD45+CD34+c-Kit+) in the bone marrow.
To model human transplantation with a briquilimab-based
conditioning regimen, humanized immune deficient mice that had been stably engrafted with human hematopoietic cells underwent a second
transplant using conditioning with briquilimab. The second human HSC graft was transduced with a lentiviral vector expressing fluorescent
mCitrine to allow assessment of its engraftment. mCitrine-marked second human donor cells were observed in all mice treated with briquilimab,
whereas no evidence of second human donor cells were found in unconditioned mice, demonstrating that briquilimab conditioning permitted
second donor HSC engraftment.
Clinical Data for Briquilimab for Severe Combined Immunodeficiency
Re-Transplantation
We have an ongoing Phase 1/2 dose escalation
open label clinical trial to evaluate briquilimab as the sole conditioning agent to achieve HSC engraftment in SCID patients
undergoing stem cell re-transplantation. The primary endpoint in Phase 1 is to assess the safety and tolerability of briquilimab as
a conditioning agent in SCID patients. The two primary efficacy endpoints defined in the Phase 2 study are the
proportion of patients achieving adequate donor HSC engraftment and the proportion of patients achieving naïve CD4+ T cell
production greater than or equal to 85 cells/uL, a level expected to provide immune reconstitution, during weeks 36 to 104
post-transplant. Secondary endpoints include durability of naïve T cell production, incidence and severity of GvHD,
hematopoietic recovery and pharmacokinetic properties of briquilimab. Patients receive a single intravenous infusion of briquilimab
on study day 0 in one of four dose cohorts: 0.1 mg/kg, 0.3 mg/kg, 0.6mg/kg or 1.0 mg/kg. Patients will be followed for five years
following transplant. This trial is currently open for enrollment at multiple clinical trial sites in the United States.
7
Other studies have shown that SCID patients who
fail to achieve durable donor cell engraftment from a first transplant may not be candidates for a second transplant using current conditioning
agents due to the toxicity of the conditioning regimen and fragile nature of most SCID patients. These patients may remain on medically
supportive immune therapies such as intravenous immunoglobulin (“IVIG”) or receive an unconditioned “boost” transplant
of donor cells which does not lead to sustained production of new immune cells.
We believe briquilimab has enabled immune reconstitution for patients
based on naïve CD4+ T-cell levels and has shown clinical benefit in T-B-SCID patients in a re-transplant setting. Patients have shown
resolution of chronic infections, independence from or reduction of IVIG therapy and antibody response to vaccine challenge. Through
December 31, 2024, in this open label clinical trial, eleven T-B-SCID re-transplant patients have been treated in the ongoing
SCID Phase 1/2 study. Seven of the eleven transplanted patients with 1- 5 years of follow-up have shown engraftment of donor
cells and production of functional immune cells. No briquilimab treatment-related “SAEs” have been reported through December
31, 2023 in this clinical trial.
The FDA has granted rare pediatric disease designation
to briquilimab as a conditioning treatment for patients with SCID. In addition, both the FDA and the European Medicines Agency (“EMA”)
have granted orphan drug designation to briquilimab for conditioning treatment prior to hematopoietic stem cell transplantation.
Stem Cell Transplant Indications
We have historically evaluated briquilimab in a number of stem cell
transplant indications, including patients with Fanconi Anemia (“FA”), Sickle Cell Disease (“SCD”), Chronic Granulomatous
Disease (“CGD”), GATA-2 MDS and others through Investigator Sponsored Trials (“ISTs”) run by partners including
the National Institute of Health (“NIH”), the National Heart, Lung, and Blood Institute, the National Institute of Allergy
and Infectious Diseases, the National Cancer Institute and Stanford University.
While promising data has been generated to date
in FA, SCD, CGD and GATA-2 MDS, given our corporate focus on mast cell driven diseases, we have discontinued these ISTs and we have no
plans to pursue additional clinical development in these indications.
Our Strategy
Our goal is to develop and commercialize briquilimab
as a safe and efficacious therapeutic to address the significant unmet medical need for patients suffering from mast cell driven diseases
such as CSU, CIndU and Asthma. As part of our strategy, we aim to:
Build a leading biotechnology company to
enable cures via immune modulation. We are bringing together a team of biotech veterans, leading academic institutions and a strong
syndicate of healthcare-focused investors to achieve our vision of developing and commercializing therapeutics with a focus on mast cell
driven diseases.
Advance the development of briquilimab
as a chronic therapeutic in mast cell driven diseases. We are focused on developing briquilimab as a repeat dose therapy for
disorders of mast cells, including CSU, CIndU, Asthma and additional mast cell driven indications currently under pre-clinical
evaluation utilizing our proprietary Jasper Mouse.
Commercialize our product candidates to expand
the use of effective and safe mast cell therapies for patients and physicians in our target markets. If approved, we plan to bring
our product candidates to the American, European and Japanese markets, focusing on the top physicians and hospital-based prescribers who
administer the majority of mast cell therapies.
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Form and strengthen strategic collaborations
with leading industry and academic organizations to further develop our pipeline, unlock the commercial potential of our portfolio and
provide enabling technologies for collaborators. We intend to continue collaborations with our existing partners and enter new
strategic partnerships to develop additional candidates, generate evidence, and commercialize new products in the field of mast cell therapies.
Agreements with Amgen
In November 2019, we entered into a worldwide exclusive
license agreement with Amgen for briquilimab (formerly AMG-191 and JSP191) in all indications and territories worldwide, which also includes
translational science and materials from Stanford University. We were assigned and accepted Amgen’s rights and obligations, effective
November 21, 2019, for the Investigator Sponsored Research Agreement (“ISRA”), entered into in June 2013, between Amgen
and The Board of Trustees of the Leland Stanford Junior University (“Stanford”) and Quality Agreement between Amgen and Stanford,
effective as of October 7, 2015. Under the ISRA, we received an option to negotiate a definitive license with Stanford for rights to certain
Stanford intellectual property related to the study of briquilimab in exchange for an option exercise fee of $1.0 million, payable over
a two-year period (the “Option”). We exercised the Option to Stanford docket S06-265 “Antibody-based clearance of endogenous
stem cell niches prior to transplantation of bone marrow or HSCs (c-kit)” granted by Stanford under the ISRA on June 2, 2020. As
a result, we have worldwide exclusive rights to develop and commercialize briquilimab in all indications, including stem cell transplants.
The issued U.S. patents would be expected to expire in 2027, absent any applicable patent term extensions.
License Agreement with Stanford
In March 2021, we entered into an exclusive license
agreement with respect to the use of briquilimab from the Stanford Office of Technology Licensing to license U.S. Patent Application Serial
Number 60/856,435, filed Nov. 3, 2006, and U.S. Patent Application Serial Number 12/447,634 (publication number US 2010/0226927 Al) and
know-how for the purpose of depleting endogenous blood stem cells in patients for whom hematopoietic cell transplantation is indicated.
Intellectual Property
Our success depends in part on our ability to obtain
and maintain proprietary protection for our product candidates and other discoveries, inventions, trade secrets and know-how that are
critical to our business operations. It also depends in part on our ability to operate without infringing the proprietary rights of others,
and in part, on our ability to prevent others from infringing our proprietary rights. We have a series of in-licensed patents outlined
below with an additional pending patent application in the United States.
In-licensed Amgen Portfolio
We have exclusively licensed a patent family from Amgen applicable
to our clinical development programs that contain patents and applications directed to humanized c-kit antibody. As of February 14, 2025,
this patent portfolio includes three issued U.S. patents and one European patent, as well as granted patents in Australia, Canada, Japan,
and Mexico, and pending patent applications in Europe and Hong Kong. The issued U.S. and European patents would be expected to expire
in 2027, absent any applicable patent term extensions.
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In-licensed Stanford Portfolio
We have an exclusive license in the field of use of briquilimab for
the purpose of depleting endogenous blood stem cells in patients for whom hematopoietic cell transplantation is indicated to a patent
family from Stanford University applicable to targeted conditioning that contains patents and applications directed to immunodepletion
of endogenous stem cell niche prior to hematopoietic stem cell transplantation. As of February 14, 2025, this patent portfolio includes
two issued U.S. patents and two European patents, as well as pending U.S., European, and Hong Kong patent applications. The issued U.S.
and European patents would be expected to expire in 2027, absent any applicable patent term extensions.
Jasper Portfolio
As of February 14, 2025, we own six patent families directed to compositions
and/or methods for hematopoietic stem cell transplantation, one patent family directed to other methods of treating certain hematopoietic
malignancies, three patent families directed to treating mast cell-driven disease, and one patent family directed to therapeutic efficacy
testing models. These patent families include two pending U.S. provisional applications, five pending U.S. utility applications, four
pending Patent Cooperation Treaty applications, and applications pending in Europe, and certain other jurisdictions. Any patents that
grant from these applications would be expected to expire in 2042 to 2046, absent any applicable patent term extensions.
Additional Intellectual Property
We also rely on trade secrets, including know-how,
confidential information, unpatented technologies and other proprietary information, to strengthen or enhance our competitive position,
and prevent competitors from reverse engineering or copying our technologies. We maintain, as trade secrets, information relating our
product candidates currently in development, as well as information related to our business strategy and business methods. However, trade
secrets and confidential know-how are difficult to protect. To avoid inadvertent and improper disclosure of trade secrets, and to avoid
the risks of former employees using these trade secrets to gain future employment, it is our policy to require employees, consultants
and independent contractors to assign to us all rights to intellectual property they develop in connection with their employment with
or services for us. We also protect our existing and developing intellectual property expressly through confidentiality provisions in
agreements with third parties. There can be no assurance, however, that these agreements will be self-executing or otherwise provide
meaningful protection for our trade secrets or other intellectual property or proprietary information, or adequate remedies in the event
of unauthorized use or disclosure of such trade secrets or other intellectual property or proprietary information. We also seek to preserve
the integrity and confidentiality of our trade secrets and other confidential information by maintaining physical security of our premises
and physical and electronic security of our information technology systems. While we have confidence in the measures we take to protect
and preserve our trade secrets, such measures can be breached, and we may not have adequate remedies for any such breach. In addition,
our trade secrets may otherwise become known or be independently discovered by competitors.
We intend to pursue additional intellectual property
protection to the extent we believe it would advance our business objectives, which may include objectives within and outside the United
States. Despite our efforts to protect our intellectual property rights these rights may not be respected in the future or may be circumvented
or challenged (and potentially invalidated) in a legal proceeding in any jurisdiction where we have intellectual property rights. In addition,
the laws of various foreign countries may not afford the same protections or assurances to the same extent as the laws in the United States.
See the section titled “Risk Factors — Risks Related to Our Intellectual Property” for additional information regarding
these and other risks related to intellectual property.
Competition
The industry we operate is in highly competitive
and dynamic, subject to rapid technological change. We have competition in the market for both our product candidates and may face competition
from large pharmaceutical and biotechnology companies, smaller pharmaceutical and biotechnology companies, specialty pharmaceutical companies,
generic drug companies, academic institutions, government agencies, research institutions and others.
We believe that our intellectual property, proprietary scientific knowledge,
development experience and partnerships will provide us with competitive advantages in the market we operate in.
We are aware of competing products and adjacent
therapies, not limited to small molecules, biologics and cell therapies, that address the same domain of conditions we are targeting.
The following list of competitors indicate companies that are directly competing with our product candidate.
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Competitors for our briquilimab c-Kit targeted
therapeutic program include the following:
Sales and Marketing
We do not currently have sales and marketing infrastructure
to support commercial launch of our product candidates, if approved. We may build such capabilities in North America prior to potential
launch of briquilimab. Outside of North America, we may rely on licensing, co-sale and co-promotion agreements with strategic partners
for the commercialization of our product candidates. If we build a commercial infrastructure to support marketing in North America, such
commercial infrastructure could be expected to include a targeted sales force supported by sales management, internal sales support, an
internal marketing group and distribution support. To develop the appropriate commercial infrastructure internally, we would have to invest
financial and management resources, some of which would have to be deployed prior to any confirmation that briquilimab will be approved.
Research and Development
We invest significantly in our research and development
efforts, to discover and validate therapeutics while improving our processes and approach to drug making. We strive to progress candidates
that can address unmet or underserved clinical needs and favor programs with well-validated targets and defined regulatory approval paths.
Our R&D team has played key roles in discovering and developing a number of promising candidates over the past 20 plus years while
at Jasper, and while at Alexion, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Genentech, Gilead, Johnson & Johnson,
Portola, and others. They have leveraged experience, insights and capabilities to optimize development, along with fostering collaboration
with external partners to innovate and expand into potential additional indications. Our current development-stage portfolio consists
of briquilimab in mast and stem cell diseases.
Manufacturing
We do not currently own or operate any manufacturing facility. We rely
on contract manufacturing organizations to produce our drug candidates in accordance with cGMP regulations for use in our clinical studies.
The manufacture of pharmaceuticals is subject to extensive cGMP regulations, which impose various procedural and documentation requirements
and govern all areas of record keeping, production processes and controls, personnel and quality control. Under our license agreement
with Amgen, we have received a substantial amount of drug product to support initiation of our planned clinical trials of briquilimab.
In November 2019, we entered into development and manufacturing agreements with Lonza Sales AG (“Lonza”) relating to the manufacturing
of briquilimab and product quality testing. The facility of Lonza in Slough, United Kingdom is responsible for production and testing
of drug substance. The facility of Lonza in Stein, Switzerland is responsible for production and testing of drug product. Labelling, packaging
and storage of finished drug product is provided by PCI Pharma Services, in San Diego, California. Our agreement with Lonza includes certain
limitations on our ability to enter into supply arrangements with any other supplier without Lonza’s consent. In addition, Lonza
has the right to increase the prices it charges us for certain supplies depending on a number of factors, some of which are outside of
our control.
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Government Regulation
Government authorities in the United States, at
the federal, state and local level, and in other countries and jurisdictions, including the European Union, extensively regulate, among
other things, the research, development, testing, manufacture, pricing, reimbursement, sales, quality control, approval, packaging, storage,
recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and import and export
of pharmaceutical products, including biological products. The processes for obtaining marketing approvals in the United States and in
foreign countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations and other regulatory authorities,
require the expenditure of substantial time and financial resources.
Licensure and Regulation of Biologics in the United States
In the United States, our product candidates are
regulated as biological products, or biologics, under the Public Health Service Act (“PHSA”) and the Food, Drug, and Cosmetic
Act (“FDCA”) and its implementing regulations and guidance. The failure to comply with the applicable U.S. requirements at
any time during the product development process, including preclinical testing, clinical testing, the approval process, or post-approval
process, may subject an applicant to delays in the conduct of the study, regulatory review, and approval, and/or administrative or judicial
sanctions.
An applicant seeking approval to market and distribute
a new biologic in the United States generally must satisfactorily complete each of the following steps:
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● payment of user fees under the Prescription Drug User Fee Act (“PDUFA”);
Preclinical Studies and Investigational New Drug Application
Before testing any biologic product candidate in
humans, the product candidate must undergo preclinical testing. Preclinical tests include laboratory evaluations of product chemistry,
formulation and stability, as well as studies to evaluate the potential for efficacy and toxicity in animal studies. The conduct of the
preclinical tests and formulation of the compounds for testing must comply with federal regulations and requirements. The results of the
preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of an IND application.
An IND is an exemption from the FDCA that allows
an unapproved product candidate 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 IND automatically becomes effective 30 days after receipt by the
FDA, unless before that time the FDA raises concerns or questions about the product or conduct of the proposed clinical trial, including
concerns that human research subjects will be exposed to unreasonable health risks. In that case, the IND sponsor and the FDA must resolve
any outstanding FDA concerns before the clinical trials can begin or recommence.
As a result, submission of the IND may result in
the FDA not allowing the trials to commence or allowing the trial to commence on the terms originally specified by the sponsor in the
IND. If the FDA raises concerns or questions either during this initial 30-day period, or at any time during the IND review process, it
may choose to impose a partial or complete clinical hold. Clinical holds are imposed by the FDA whenever there is concern for patient
safety, may be a result of new data, findings, or developments in clinical, preclinical, and/or chemistry, manufacturing, and controls
or where there is non-compliance with regulatory requirements. This order issued by the FDA would delay either a proposed clinical trial
or cause suspension of an ongoing trial, until all outstanding concerns have been adequately addressed and the FDA has notified the company
that investigations may proceed. This could cause significant delays or difficulties in completing our planned clinical trial or future
clinical trials in a timely manner.
Human Clinical Trials in Support of a BLA
Clinical trials involve the administration of the
investigational product candidate to healthy volunteers or patients with the disease or condition to be treated under the supervision
of a qualified principal investigator in accordance with GCP requirements. Clinical trials are conducted under protocols detailing, among
other things, the objectives of the trial, inclusion and exclusion criteria, the parameters to be used in monitoring safety, and the effectiveness
criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part
of the IND.
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A sponsor who wishes to conduct a clinical
trial outside the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. When a
foreign clinical trial is conducted under an IND, all FDA IND requirements must be met unless waived. When a foreign clinical trial
is not conducted under an IND, the sponsor must ensure that the trial complies with certain regulatory requirements of the FDA in
order to use the trial as support for an IND or application for marketing approval. Specifically, the FDA requires that such trials
be conducted in accordance with GCP, including review and approval by an independent ethics committee and informed consent from
participants. The GCP requirements encompass both ethical and data integrity standards for clinical trials. The FDA’s
regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical trials, as well as the
quality and integrity of the resulting data. They further help ensure that non-IND foreign trials are conducted in a manner
comparable to that required for clinical trials in the United States.
Further, each clinical trial must be reviewed and
approved by an IRB either centrally or individually at each institution at which the clinical trial will be conducted. The IRB will consider,
among other things, clinical trial design, patient informed consent, ethical factors, the safety of human subjects, and the possible liability
of the institution. An IRB must operate in compliance with FDA regulations. The FDA, IRB, or the clinical trial sponsor may suspend or
discontinue a clinical trial at any time for various reasons, including a finding that the clinical trial is not being conducted in accordance
with FDA requirements or that the participants are being exposed to an unacceptable health risk. Clinical testing also must satisfy extensive
GCP rules and the requirements for informed consent.
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 (“DSMB”)
or Independent Data Safety Monitoring Committee (“IDMC”). This group may recommend continuation of the trial as planned, changes
in trial conduct, or cessation of the trial at designated check points based on certain available data from the trial to which only the
DSMB or IDMC has access.
Clinical trials typically are conducted in three
sequential phases, but the phases may overlap or be combined. Additional studies may be required after approval.
In some cases, the FDA may approve a BLA for a product but require
the sponsor to conduct additional clinical trials to further assess the product’s safety and effectiveness after licensure. Such
post-approval studies are typically referred to as Phase 4 clinical trials. These studies are used to gain additional experience from
the treatment of patients in the intended therapeutic indication and to document a clinical benefit in the case of biologics approved
under accelerated approval regulations. The FDA may require a post-approval study to be underway prior to approval or within a specified
time period following approval, and the submission of progress reports for the study. The FDA is authorized to initiate enforcement action
for the failure to conduct with due diligence a required post-approval study, including a failure to meet any required conditions specified
by the FDA or to submit timely reports. If the FDA approves a product while a company has ongoing clinical trials that were not necessary
for approval, a company may be able to use the data from these clinical trials to meet all or part of any Phase 4 clinical trial requirement