JSPR US Equity☆

Item 1A. Risk Factors. 35

Item 1B. Unresolved Staff Comments. 94

Item 2. Properties. 94

Item 3. Legal Proceedings. 94

Item 4. Mine Safety Disclosures. 94

PART II

Item 6. [Reserved]. 95

Item 7A. Quantitative and Qualitative Disclosures About Market Risk. 114

Item 8. Financial Statements and Supplementary Data. 114

Item 9A. Controls and Procedures. 149

Item 9B. Other Information. 149

PART III

Item 10. Directors, Executive Officers and Corporate Governance. 150

Item 11. Executive Compensation. 150

Item 14. Principal Accountant Fees and Services. 151

PART IV

Item 15. Exhibit and Financial Statement Schedules. 151

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 (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.

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 ability to maintain the listing of our public securities on Nasdaq;

● our public securities’ potential liquidity and trading;

1

● our ability to grow and manage growth profitably;

● our ability to identify, in-license or acquire additional technology;

● the effect of the continuing COVID-19 pandemic on the foregoing.

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. Some of these risks and uncertainties may in the

future be amplified by the continuing COVID-19 pandemic, and 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.

2

PART

I

ITEM

1. BUSINESS

Overview

We

are a clinical-stage biotechnology company dedicated to enabling cures through hematopoietic stem cell therapy. We are focused on the

development and commercialization of safer and more effective conditioning agents and stem cell engineering to allow for expanded use

of stem cell transplantation and ex vivo gene therapy, a technique in which genetic manipulation of cells is performed outside of the

body prior to transplantation.

Our

drug development pipeline includes multiple product candidates designed to improve hematopoietic stem cell therapy. Our lead product

candidate, JSP191, is in clinical development as a novel conditioning antibody that clears hematopoietic stem cells from bone marrow

in patients prior to undergoing allogeneic stem cell therapy or stem cell gene therapy. We are also developing engineered hematopoietic

stem cells (“eHSC”) product candidates reprogrammed using mRNA delivery and gene editing that have a competitive advantage

over endogenous hematopoietic stem cells (“HSCs”) because they permit higher levels of engraftment without the need for toxic

conditioning of the patient and with potentially lower risk of other serious complications seen with current stem cell transplants. We

also plan to continue to expand our pipeline to include other novel stem cell therapies based on immune modulation, graft engineering

or cell and gene therapies. Our goal is to expand the use of curative stem cell transplant and gene therapies for all patients, including

children and the elderly.

Stem cell transplantation is among the most widely

practiced forms of cellular therapy and has the potential to cure a wide variety of diseases, including cancers, genetic disorders and

autoimmune diseases. A stem cell transplant procedure involves three main steps: (i) stem cells from the patient’s or donor’s

bone marrow are collected; (ii) the patient’s bone marrow is cleared of any remaining stem cells in order to make space to receive

new transplanted stem cells, which is known as conditioning; and (iii) the new stem cells are transplanted into the patient via infusion

where they fasten to, or engraft in, the bone marrow and grow into the blood and immune cells that form the basis of reset and rebuilt

blood and immune systems. Transplants are either allogeneic or autologous, depending on the source of the new stem cells for the transplant.

In an allogeneic transplant, patients receive cells from a stem cell donor. In an autologous transplant, the patient’s own stem

cells are used. Autologous transplants also include stem cell gene therapies, where cells are collected from the patient, edited to either

enable a functioning gene or correct a defective gene, and then transplanted into the patient via infusion. Our programs span both allogeneic

and gene therapy-based autologous transplants, with initial sponsored programs in JSP191 based on an allogeneic approach.

Currently,

patients must receive highly toxic and potentially life-threatening conditioning agents to prepare their bone marrow for transplantation

with either donor stem cells or their own gene-edited stem cells. Younger, fitter patients capable of surviving these toxic side effects

are typically given myeloablative, or high-intensity, conditioning whereas older or less fit patients are typically given reduced intensity,

but still toxic, conditioning which leads to less effective transplants. These toxicities include a range of acute and chronic effects

to the gastrointestinal tract, kidneys, liver, lung, endocrine, and neurologic tissues. Depending upon the conditioning regimen, fitness

of the patient, and compatibility between the donor and recipient, the risk of transplant-related mortality ranges from 10% to more than

50% in older patients. Less toxic ways to condition patients have been developed to enable transplant for older patients or those with

major comorbidities, but these regimens risk less potent disease elimination and higher rates of disease relapse. Even though stem cell

therapy can be one of the most powerful forms of disease cure, these limitations of non-targeted conditioning regimens have seen little

innovation over the past decade.

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Our lead product candidate, JSP191, is a monoclonal antibody designed

to block a specific survival signal on stem cells and is in development as a highly targeted conditioning agent prior to stem cell therapy.

We are developing JSP191 for severe combined immunodeficiency (“SCID”) for which we are currently conducting an open label

Phase 1/2 clinical trial in two cohorts of SCID patients: patients with a history of a prior allogeneic transplant for SCID but with poor

graft outcomes and newly diagnosed SCID patients. The primary endpoint in Phase 1 is to evaluate the safety and tolerability of JSP191.

The two primary efficacy endpoints in Phase 2 are the proportion of subjects achieving adequate donor HSC engraftment and the proportion

of subjects achieving naïve 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. Based on preliminary results from our ongoing Phase 1/2 clinical trial, we believe JSP191 has

demonstrated the ability as a single agent to enable engraftment of donor HSCs as determined by donor chimerism, or the percentage of

bone marrow cells in the patient that are of donor origin after transplant. Six out of the first nine non-IL2RG patients with prior allogeneic

transplant achieved donor engraftment, naïve donor T cell production and demonstrated clinical improvement. No JSP191 treatment-related

serious adverse events (“SAEs”) have been reported to date and pharmacokinetics have been consistent with earlier studies

in healthy volunteers. We expect to complete enrollment in this Phase 1/2 clinical trial by mid-2023.

The

FDA has granted rare pediatric disease designation to JSP191 as a conditioning treatment for patients with SCID. In addition, the FDA

granted orphan drug designation to JSP191 for conditioning treatment prior to hematopoietic stem cell transplantation.

We also are evaluating JSP191 in an open label Phase 1 clinical trial

in patients with myelodysplastic syndrome (“MDS”) or acute myeloid leukemia (“AML”) that were transplant eligible

but still had trace evidence of leukemic cells that can remain in a patient after chemotherapy, or minimal residual disease (“MRD”),

as detected by cytogenetics, flow cytometry or next-generation sequencing. The primary endpoints are to evaluate the safety, tolerability

and pharmacokinetic parameters of JSP191. In the initial dose finding Phase 1a portion of this clinical trial, 0.6 mg/kg JSP191-based

conditioning was well tolerated in all six MDS/AML patients as of December 31, 2021. Furthermore, it led to successful engraftment as

demonstrated by sustained blood neutrophil count of >500 x 10^6 / L (Wolff 2002) in all six patients. Additionally, five of the six

patients demonstrated elimination of all diseased cells at day 90 (MRD) by multiple methods of detection, a secondary endpoint of the

clinical study. The next portion of the clinical trial, a Phase 1b dose expansion cohort has completed enrollment. Initial results from

the first seventeen patients show that 0.6 mg/kg JSP191-based conditioning was well tolerated with all seventeen patients achieving successful

engraftment. These initial results also show that twelve of fifteen Phase 1a and 1b patients with MRD at screening achieved clearance

of MRD. No JSP191-related serious adverse events have been reported. As of reporting of these initial results, four patients have come

off study, two due to relapse or disease progression, one due to late onset Grade 3 acute Graft vs Host Disease (“GvHD”) and

one due to secondary graft failure. We expect to present additional data from this study in the first half of 2022.

4

We have entered into a clinical collaboration with Stanford University

to study JSP191-based conditioning in patients with Fanconi anemia. This study is currently open for patient recruitment. We are also

collaborating with the National Institutes of Health to conduct clinical trials of JSP191-based conditioning in patients with sickle cell

disease (“SCD”), with chronic granulomatous disease and with GATA-2 mutated MDS. We believe that JSP191 may also be useful

for conditioning in allogenic transplant for other diseases beyond which we are currently studying, including autoimmune diseases. We

also believe that targeted JSP191-based conditioning may improve the efficacy and safety of gene therapies. We are also collaborating

with corporate partners, including Graphite Bio, Inc. (“Graphite Bio”), Aruvant Sciences GmbH (“Aruvant Sciences”)

and AVROBIO, Inc. (“Avrobio”) to study JSP191 as targeted, non-toxic conditioning for investigational gene therapies.

We plan to evaluate JSP191 as a therapeutic for

certain patients with proliferative disorders of the hematopoietic stem cell. MDS is a heterogeneous disorder of the bone marrow which

typically occurs in an older population and can progress to AML. The Revised International Prognostic Scoring System (“IPSS-R”)

is a clinical assessment tool used to evaluate risk and prognosis of newly diagnosed patients. Patients with IPSS-R scores of low or

very low are not typically referred to stem cell transplant due to the risk of transplant-related toxicities from current conditioning

regiments, infection and GvHD outweighing the patient’s expected survival with drug therapies. These patients typically suffer

from anemia, thrombocytopenia or neutropenia and are given drug therapies such as an erythropoiesis stimulating agent (“ESA”)

to stimulate production of new cells to correct their blood deficiency. However, these agents do not target the diseased hematopoietic

stem cell and patients who become refractory to ESA are dependent on routine blood transfusions, which is associated with poor survival.

ESA-refractory low-risk MDS patients have few treatment options and are a clinical unmet need.

JSP191 and other anti-CD117 monoclonal antibodies

have been shown to deplete normal and diseased MDS human hematopoietic stem cells in clinical and pre-clinical studies. In studies of

non-human primates and healthy volunteers, administration of a single dose of JSP191 resulted in depletion of healthy hematopoietic stem

cells followed by recovery in approximately six weeks. Additional recent clinical data in MDS patients undergoing stem cell transplant

showed depletion of hematopoietic stem cells after administration of JSP191 alone. By depleting diseased and healthy hematopoietic stem

cells, we believe that JSP191 may allow for preferential recovery of healthy hematopoietic stem cells and restoration of normal hematopoiesis.

We intend to study JSP191 monotherapy in low-risk MDS patients with documented cytopenia who are refractory to ESA therapy.

Our eHSC platform is designed to overcome key

limitations of stem cell transplant and stem cell gene therapy. By using mRNA delivery and/or gene editing, we believe we can reprogram

donor or gene corrected stem cells to have a transient proliferative and survival advantage over the patient’s existing cells.

We believe initial preclinical experiments by Jasper demonstrate multiple different mRNAs can be used to improve engraftment of modified

stem cells. One example are eHSCs that express certain variants of CXCR4 that may lead to improved stem cell homing and engraftment in

the bone marrow. Another example includes expression of a modified stem cell factor receptor that can lead to cell line proliferation

independent of stem cell factor (“SCF”) concentration, enabling our eHSCs to outcompete unmodified HSCs through better survival

and engraftment. Also, since JSP191 only blocks signaling through the stem cell factor receptor, these eHSCs are not affected by JSP191

when used in combination. Other initial experiments have shown that mRNA can be used to express these receptor variants on the cell surface.

We have also identified other potential receptor modifications that prevent the binding of JSP191 but retain the ability to bind SCF,

therefore allowing the eHSCs to proliferate normally even in the presence of JSP191.

We

intend to become a fully integrated discovery, development and commercial company in the field of hematopoietic stem cell therapy. We

are developing our product candidates to be used individually or, in some cases, in combination with one another. As a result, we believe

our pipeline could be tailored to the patient-specific disease so that a patient may receive more than one of our therapies as part of

his or her individual allogeneic or gene-edited stem cell therapy. 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 advance our pipeline and innovate through our research platform.

We

have an exclusive license agreement with Amgen Inc. (“Amgen”) for the development and commercialization of the JSP191 monoclonal

antibody in all indications and territories worldwide. We also have an exclusive license agreement with Stanford for the right to use

JSP191 in the clearance of stem cells prior to the transplantation of HSCs. We also entirely own the intellectual property for our eHSC

platform, which has been internally developed.

Our Product

Pipeline

We

are developing a portfolio of novel product candidates that we believe have the potential to meaningfully improve stem cell therapy for

patients with blood cancers, genetic diseases and autoimmune diseases. Additionally, we believe our product candidates have the potential

to allow more patients with debilitating or life-threatening diseases to access a one-time, transformative blood and immune reset through

transplant with better outcomes and reduced risk of toxicity and mortality versus current technologies. We are developing our product

candidates so that they can be used individually or in combination with one another, such that patients may receive more than one of

our therapies as part of their individual transplant journey. In addition to our first set of clinical product candidates, we are in

the process of identifying several other potential candidates from our engineered hematopoietic stem cell platform.

5

The following chart summarizes the status and

development plan for the product candidates in our pipeline. We own worldwide rights to each of our programs.

JSP191

We

believe JSP191 is a unique, humanized, monoclonal antibody that targets the underlying biology of hematopoietic stem cells to potentially

improve the efficacy and safety of hematopoietic stem cell transplantation. JSP191 is in clinical development as a conditioning agent

to clear hematopoietic stem cells from the bone marrow prior to transplant. JSP191 binds to human CD117, a receptor for SCF, which is

expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive.

By blocking SCF from binding to CD117 and disrupting critical survival signals, JSP191 leads to the depletion of stem cells and creates

an open space in the bone marrow for donor or gene-edited stem cells to engraft. JSP191 is in clinical development both as a single conditioning

agent and in combination with existing conditioning agents depending on the need in a particular indication.

Engineered

Hematopoietic Stem Cells

Our eHSCs are designed to overcome key limitations of allogeneic donor

and autologous gene-edited stem cell transplants. By delivering mRNA or modifying DNA, leading to expression of a modified receptor or

protein, we can reprogram donor or gene-edited stem cells to have a transient proliferative and survival advantage over the patient’s

existing cells to permit higher levels of engraftment without the need for toxic conditioning of the patient. eHSCs have the potential

to eliminate the need for donor T-cells, B-cells and NK-cells which are needed in unmodified donor HSC grafts to permit robust engraftment

but can lead to GvHD, where the donor cells attack the patient’s tissues, resulting in the need for long-term immunosuppression

therapies.

Our Strategy

Our

goal is to bring curative allogeneic and autologous HSCT and gene therapy to more people by developing compounds that can make it safer

and more effective. As part of our strategy, we aim to:

Build

a leading HSCT biotechnology company to enable cures via immune modulation, graft engineering and cell and gene therapies. 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 an improved end-to-end stem cell transplantation process and associated therapies, starting with

safer and more effective conditioning agents and engineered stem cell therapies.

6

Continue to develop JSP191 as a novel, targeted

pre-transplant conditioning agent enabling more efficacious and safer HSCT. Starting with our lead product candidate, JSP191,

we are advancing the field of HSCT to address effective and safe pre-transplant conditioning in hematologic monogenic and malignant disorders

as well as in autoimmune disease and gene therapy. Our initial focus is on severe combined immunodeficiency, acute myeloid leukemia,

myelodysplastic syndrome and autologous gene-edited stem cell transplants.

Advance our eHSC platform to overcome the

limitations of current allogeneic and autologous gene-edited stem cell transplants. We are developing enhanced stem cell therapies

with transient proliferative advantages, which we believe may translate to superior efficacy and reduced GvHD compared to current standard

of care therapies in allogenic and autologous gene therapy transplants.

Commercialize

our product candidates to expand the use of effective and safe stem cell therapies for patients and physicians in our target markets.

If approved, we plan to bring our product candidates to the United States, European and Japanese markets, focusing on the top

50% of accredited transplant centers and hospital-based prescribers who administer approximately 80% of stem cell therapies. Our strong

network and relationships with key stakeholders at these centers will enable a targeted and collaborative commercial approach.

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 gene therapy 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 stem cell therapy.

Our History

and Team

Old

Jasper was founded by Dr. Judith Shizuru, Professor of Medicine and Pediatrics at Stanford University, and Dr. Susan Prohaska, a Stanford-trained

immunologist, stem cell biologist and drug developer, with the goal of bringing curative hematopoietic stem cell transplantation to more

people by making it safer and more effective. We unite technologies from Stanford University and Amgen via expertise in stem cell transplantation,

stem cell biology and drug development. Building on bone marrow niche-clearing technology from Stanford and with our lead compound JSP191,

Dr. Shizuru initiated a clinical program funded by the California Institute for Regenerative Medicine (“CIRM”) to safely

condition patients with SCID prior to hematopoietic cell transplantation.

We

have assembled a management team of experienced biopharma industry veterans. With this leadership, we believe we are well positioned

to achieve our vision of revolutionizing hematopoietic cell transplantation with safer conditioning regimens. Ron Martell, our Chief

Executive Officer, is an experienced biopharma veteran who has extensive experience in cellular therapies and oncology drug development.

Prior to joining Jasper, Mr. Martell served as the President and CEO of MorphImmune, Inc., a private platform company advancing a highly

specific targeting technology that uses a ligand-linked payload to reprogram the immune system. Previously, he was President and CEO

of Nuvelution Pharma. He was also Co- Founder and Executive Chairman of Indapta, Orca Bio and Co-Founder and CEO of Achieve Life Sciences,

where he led the merger of the company with Oncogenex. Mr. Martell has served as the CEO of three public biopharmaceutical companies,

including Sevion and NeurogesX, and has overseen billions of dollars in industry transactions. Earlier in his career, Martell served

as Senior Vice President of Commercial Operations at ImClone Systems, where he was instrumental in deals with Bristol-Myers Squibb and

Merck KGaA and built ImClone Systems’ worldwide operations to market and commercialize Erbitux®. He also served in various leadership

positions with Genentech where, as Group Manager, Oncology, he was responsible for building the company’s oncology franchise, including

the launch of Herceptin® and Rituxan®.

Members

of our management team have held leadership positions at companies that have successfully discovered, developed, and commercialized therapies

for various cancers and devastating rare diseases. These companies include Roche, Johnson & Johnson, Genentech, Bristol-Myers Squibb,

Imclone, Incyte, Allergan, Sanofi, Amgen, Portola, Alexion and many others.

7

Background

on Hematopoietic Stem Cell Therapy

HSCT

is among the most widely practiced forms of cellular therapy and has the potential to cure a wide variety of diseases. Currently, its

use is limited to patients with severe disease burden due to the toxicities of current non-targeted conditioning regimens and the limitations

of the transplant grafts themselves.

Stem

cell transplants first require identification of a suitable donor and collection of the donor’s stem cells, typically from blood.

Then chemotherapy or radiation-based conditioning is used to clear the patient’s bone marrow of existing diseased stem cells in

order to make space to receive new transplanted stem cells. Finally, the donor or gene corrected stem cells are infused into the patient

where they engraft into the bone marrow and produce new blood and immune cells that form the basis of a reset and rebuilt blood and immune

system. All transplants are categorized as either autologous or allogeneic, depending on the source of the new stem cells for the transplant.

In

an autologous transplant, which is used for conditions such as multiple myeloma, non-Hodgkin’s lymphoma and certain autoimmune

diseases, the patient’s own stem cells are used. Autologous transplants also include stem cell gene therapies, in which cells are

collected from the patient, edited to either insert a functioning gene into, or correct a defective gene within, such cells and then

such cells are transplanted into the patient via infusion.

In

an allogeneic transplant, used for conditions such as acute leukemias, myelodysplastic syndromes, genetic diseases and certain autoimmune

diseases, patients receive cells from a stem cell donor. The preferred donor is a biological relative who has a well-matched immune system.

The second option is a matched unrelated donor identified through a bone marrow donor registry. Transplant outcomes are not optimal with

mismatched donors.

Current

State of Conditioning Regimens

Currently, patients must receive highly toxic,

potentially life-threatening and non-specific conditioning agents to prepare their bone marrow for transplantation with either donor

stem cells or their own gene-edited stem cells. Current conditioning agents are genotoxic and are associated with major toxicities and

adverse events such as oral mucositis, sepsis, veno-occlusive disease, bacteremia, pulmonary fibrosis, and GvHD in the near term. In

the long term, patients must be counseled against risk of infertility of up to 70% and risk of secondary cancers of 5-10% after chemotherapy

conditioning. Additionally, there is a treatment-related mortality risk associated with current conditioning regimens that ranges from

10% to more than 50% in older patients. Other limitations of chemotherapy-based conditioning include incomplete engraftment, transplant

ineligibility and prolonged hospitalization.

8

Current

State of Hematopoietic Stem Cell Grafts

Hematopoietic stem cell grafts currently have limitations

around failed or poor engraftment with the risk of clinical relapse. Furthermore, GvHD is a high-risk short- and long-term adverse event

associated with HSCT as a result of donor T-cells, B-cells and NK-cells which are needed in unmodified donor HSC grafts to permit robust

engraftment. Donor immune cells may react to the patient’s tissues as foreign leading to GvHD whereas newly produced immune cells

are trained by the patient’s body to not act against the patient’s own cells. Due to this risk, patients also need to undergo

long-term immunosuppression.

Our Solution

and Product Candidates

We

are developing a conditioning agent that could significantly expand the eligible patient population for both allogeneic and autologous

gene edited hematopoietic stem cell therapies in addition to engineered hematopoietic stem cells that could result in better transplant

efficacy with reduced complications. Currently, approximately 20,000 patients receive allogeneic and autologous gene therapy transplants

each year in the major global markets (the United States, the United Kingdom, France, Germany, Spain, Italy and Japan), and we believe

this may grow to 80,000 patients with safe conditioning and more effective grafts.

JSP191

is a targeted anti-CD117 (stem cell factor receptor) antibody which we are currently evaluating in two clinical trials for conditioning

prior to stem cell transplant in patients with SCID, MDS or AML. JSP191 is designed to bind to CD117 with a greater affinity than SCF.

By blocking signaling of the stem cell factor receptor, JSP191 leads to depletion of stem cell from the bone marrow. JSP191 was also

designed to minimize any interaction with the immune system thereby reducing the risk of immune activation via mast cells or other pathways

normally activated by antibodies.

We

believe these attributes will allow JSP191 to potentially be used as a monotherapy or in combination to deplete normal and diseased stem

cells. The blocking of SCF by JSP191 may remove a critical survival signal on stem cells that leads to their depletion in the bone marrow.

Other cells (mast cells, Cajal cells, germ cells, melanocytes) that express CD117 are less dependent on SCF signaling for survival and

do not appear to be significantly affected by a single administration of JSP191. Furthermore, the mechanism of action (“MOA”)

of JSP191 on stem cells may be synergistic with other disruptors of stem cell survival such as radiation, azacytidine, and CD47. Our

MDS/AML clinical strategy aims to exploit this biology to safely clear both diseased and normal stem cells prior to transplantation of

donor cells.

The

monoclonal antibody isotype and other modifications of JSP191 were also chosen carefully to retain high affinity binding to the CD117

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, simply changing JSP191 from an IgG1 isotype to an IgG2 isotype would result in less potent

inhibition of CD117, potentially decreasing the effect on stem cell depletion. This finding and other data demonstrate that not all anti-CD117

antibodies behave equally or have the same MOA.

Other

known approaches to target CD117, such as anti-CD117 antibodies linked to a toxin, may have off-target toxicity. In contrast to JSP191,

which provides a transient SCF signal blockade, a toxin linked anti-CD117 antibody requires internalization by CD117 expressing cells

leading to cell death. Any CD117 expressing cell including stem cells, mast cells, germ cells and melanocytes may be affected by this

mechanism. Furthermore, the complexity of an antibody-drug conjugate molecule adds to the manufacturing, clinical and regulatory risks

of the drug development process, especially for a novel linker/payload combination that may be subject to different regulatory and Chemistry,

Manufacturing and Controls (“CMC”) reviews.

9

Preclinical

Data for JSP191 — General

We

conducted a preclinical study to determine if non-human primate (“NHP”) HSCs are sufficiently similar to human HSCs to allow

use of the same phenotype assays used in human studies to evaluate the effect of JSP191 on NHP hematopoiesis. This study tested, by flow

cytometry, a technique used to measure physical and chemical characteristics of a population of cells, whether homologous subsets of

NHP bone marrow express the same cellular markers as human HSCs (CD34, CD90, and CD117), and if the human antibody reagents used to identify

these markers could also be used for NHP HSCs. Bone marrow samples (or bone marrow aspirates) of NHPs and humans were stained with the

antibody reagents directed against human CD34, CD90, and CD117. HSCs in both human and NHP bone marrow were phenotypically identified

using the anti-human antibodies against CD34 and CD90. A high percentage of human and NHP cells expressing CD34 and CD90 (also CD34+

and CD90+) also express CD117. Overall, we believe these data support the use of human antibody reagents for CD34 and CD90 to assess

the effect of JSP191 on hematopoiesis in NHP in vitro and in vivo studies.

Figure

1: JSP191 binds CD117 on CD34+CD90- and CD34+CD90+ cells in human and NHP bone marrow. Left panel: flow cytometric analysis of HSCs fluorescently

labelled for CD34 and CD90. Right panel: the identified CD34+CD90- and CD34+CD90+ cells are then fluorescently labelled with 104D2 and

JSP191. JSP191 and 104D2 non-competitively labeled the same population suggesting these antibodies bind different epitopes of NHP and

human CD117.

10

Non-clinical

studies in NHPs conducted at Stanford by Hye-Sook Kwon, Ph.D., now Principal Scientist at Jasper, demonstrated JSP191’s ability

to deplete bone marrow HSCs in a large animal model (Figure 2). Non-clinical studies in “humanized” mice demonstrated both

depletion of human HSCs and engraftment of allogeneic donor HSCs. These studies supported the potential for JSP191 to deplete human stem

cells prior to stem cell transplant in the IND filings for the ongoing clinical trials designed to assess the safety and efficacy of

JSP191 in HSC transplant for SCID and MDS/AML.

Figure

2: Representative flow cytometry analysis for cells fluorescently labeled with CD34 and CD90 on days 0, 10, and 42 post administration

of 1.0 mg/kg JSP191. CD34+ stem cells in the bone marrow of this NHP are transiently depleted. HSC depletion lasted up to 21 days in

most animals and more than 42 days in one NHP receiving the highest dose.

11

JSP191

for Acute Myeloid Leukemia and Myelodysplastic Syndrome

AML

is a cancer of the blood and bone marrow, diagnosed in about 42,000 patients annually within the major global markets. It is primarily

a disease of the elderly and is the most common type of acute leukemia diagnosed in adults. Patients with AML are deemed eligible for

stem cell transplantation based on criteria which includes patient fitness (age and comorbidities) and response to initial treatment,

comprising of about 40% of newly diagnosed AML patients. However, stem cell transplants are administered to approximately 40% of the

eligible patient population due to current challenges with highly toxic conditioning regimens. Currently, approximately 8,000 patients

with AML receive a stem cell transplant annually in the major global markets.

MDS

is a group of disorders of the bone marrow where hematopoietic stem cells fail to properly differentiate into mature blood cells, leading

to low blood cell count. Approximately 29,000 patients are diagnosed with MDS annually in the major global markets. Of all newly diagnosed

MDS patients, about 35% have mid to high-risk disease and about 30% of those are eligible for HSCT based on age, comorbidities and blast

count. However, about 60% of MDS patients who are otherwise eligible receive a transplant due to the current challenges with highly toxic

conditioning regimens. Currently, approximately 2,500 patients with MDS receive HSCT each year.

Hematopoietic

stem cell transplantation offers the only known potentially curative therapy for many forms of AML and for MDS. Standard of care conditioning

regimens can be divided into three groups: myeloablative conditioning, reduced intensity conditioning and non-myeloablative conditioning.

Myeloablative conditioning with high dose busulfan, high dose melphalan or high dose radiation is the most aggressive approach and is

associated with the lowest rates of disease relapse. However, due to significant toxicities, including treatment related mortality, this

approach is reserved for the most fit and younger patients. Reduced intensity conditioning with lower dose busulfan or lower dose melphalan

can be used for a wider group of patients, but due to substantial toxicities, many patients remain ineligible. Non-myeloablative conditioning

with low dose radiation (200 – 450 cGy, or centigray, a unit of radiation of exposure) is well tolerated but is associated with

lower rates of successful donor chimerism and increased relapse rates compared to myeloablative or reduced-intensity conditioning.

Due

to their age and co-morbidities, older (60 years and older) and less fit MDS and AML patients are typically unable to tolerate more intensive

therapy and the toxicities associated with such treatments, and thus, have a worse prognosis than younger, fitter patients. Thus, safe

and effective conditioning prior to HSCT represents an unmet medical need for MDS and AML patients.

Preclinical

Data for JSP191 for Myelodysplastic Syndrome

Preclinical

studies of immune deficient mice engrafted with MDS HSCs from patients with “high-risk and very high-risk disease” per Revised

International Prognostic Scoring System (“R-IPSS”) criteria conducted at Stanford by Wendy Pang, M.D., Ph.D., now Vice President

of Research and Translational Medicine at Jasper, demonstrate the utility of anti-CD117 antibodies in the treatment of MDS. Mice xenografted

with high-risk MDS HSCs were treated with anti-human CD117 monoclonal antibody (“mAb”), SR-1 (the parent clone to JSP191).

Initial studies showed administration of either SR-1 or JSP191 resulted in well-tolerated and sustained depletion of MDS cells obtained

from low-risk MDS patients. Treatment of mice xenografted with high-risk MDS HSCs cells resulted in transient depletion (Figure 3). Given

the transient depletion of high-risk MDS cells, studies were conducted to determine whether an anti-CD117 antibody followed by a normal

human HSC allograft would lead to long-term disease amelioration of high-risk disease. Results showed greater than 95% cytogenetically

normal CD45+ cells 12 weeks after allograft transplant (Figure 3).

Figure

3: (A) CD117 mAb depletes MDS stem cells as demonstrated by decreasing HSC chimerism over time. (B) Normal stem cell engraftment occurs

after stem cell depletion as shown by greater than 95% cytogenetically normal CD45+ cells 12 weeks after transplant in four high-risk

MDS-xenografted mice. (C) Normal blood formation results after stem cell engraftment with human cell lineages for T cells (CD3+), B cells

(CD19+) and myeloid cells (CD13/33+) in the bone marrow of the four high-risk mice.

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Mice

xenografted with MDS HSCs from low-risk or high-risk patients were treated with SR-1 concurrently with an anti-mouse CD117 mAb, ACK2,

to suppress endogenous mouse HSCs, and then transplanted with normal human UCB. Twelve weeks after this UCB HSC transplantation, both

human myeloid and lymphoid cells like T cells and B cells were observed in the bone marrow (Figure 3), indicative of successful engraftment

and sustained hematopoiesis by healthy UCB HSCs for both risk categories. Fluorescence in situ hybridization studies assessing clonal

cytogenetic abnormalities confirmed that human CD45+ cells in both groups were predominantly (greater than 95%) cytogenetically normal

in all SR-1 treated and UCB HSC engrafted mice. In contrast, MDS xenografted mice treated with the control antibody showed a persistence

of high levels of MDS cells (greater than 95%) and were without second donor HSC engraftment.

Clinical

Data for JSP191 for Acute Myeloid Leukemia and Myelodysplastic Syndrome

We

have an ongoing open label Phase 1 clinical trial to evaluate the safety and tolerability of JSP191 conditioning, in combination with

low dose radiation (200-300 cGy) and fludarabine, in patients with AML or MDS undergoing blood stem cell transplantation. At clinical

trial entry for the dose finding portion, all patients were transplant eligible but most still had evidence of measurable residual disease

(MRD positive) as detected by cytogenetics, flow cytometry or next-generation sequencing. The starting dose of JSP191 is 0.6 mg/kg with

potential escalation up to 1.0 mg/kg, fludarabine is administered at 30 mg/m2/day on transplant days -4, -3, and -2 and total body irradiation

(“TBI”) is delivered at 200 or 300 cGy on the day of transplant. The primary endpoints are to evaluate the safety, tolerability

and pharmacokinetic parameters of JSP191. Secondary endpoints include depletion of host HSCs, donor engraftment, donor chimerism, MRD

clearance, non-relapse mortality, event-free survival and overall survival. Enrolled patients will be followed for one year. The overall

study duration is anticipated to be approximately two years.

In

the initial dose finding Phase 1a portion of this clinical trial, 0.6 mg/kg JSP191-based conditioning was well tolerated in all six MDS/AML

patients as of December 31, 2021. All six patients demonstrated evidence of successful depletion of host HSCs, observed by a reduction

of neutrophil counts (“ANC”) below 500/uL following a single infusion of JSP191 (0.6 mg/kg) in combination with 200 cGy TBI

and three days of 30 mg/m2/day fludarabine. Neutrophils are the most common type of white blood cell and are the first cells to engraft.

Following transplant, all six patients showed successful donor engraftment as evidenced by a recovery of neutrophil counts exceeding

500/uL in 19 to 26 days (Figure 4).

Figure

4: Neutrophil depletion and recovery in the first six patients of the Phase 1 MDS/AML clinical trial. All six of these initial patients

demonstrated ANC greater than 500/uL within 19 to 26 days after transplant.

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At

90 days following transplant, five of six patients demonstrated 95% or greater total donor chimerism levels as measured by CD15,

CD3 and CD56 assays. In addition, five of six patients no longer had evidence of MRD at day 90. Total donor chimerism of 95% or greater

and change in MRD status from positive to negative are both associated with reduced risk of disease relapse.

The next portion of the clinical trial,

a Phase 1b dose expansion cohort, has recently completed enrollment. Initial results from the first seventeen Phase 1a and Phase 1b patients

show that 0.6 mg/kg JSP191-based conditioning was well tolerated with all seventeen patients achieving successful engraftment. As of Day

90, each of the fourteen evaluable Phase 1a and 1b subjects achieved full myeloid donor chimerism (mean 98.4 ± 1.2%). Ten of twelve Phase 1a and 1b patients with MRD prior to transplant

no longer had evidence of MRD at Day 90. As of reporting of these initial Phase 1a and 1b results, four patients have come off study,

two due to relapse or disease progression, one due to late onset Grade 3 acute GvHD and one due to secondary graft failure (Figure 5).

Figure

5: JSP191 MDS/AML Phase 1 preliminary clinical results in the first seventeen patients. The clinical trial cohorts consisted AML/MDS

patients not eligible for standard myeloablative regimens (HCT-Cl greater than 2).

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No JSP191 related SAEs have been reported, including

no cases of oral mucositis, no cases of veno-occlusive disease. One case of grade 3 late onset GI GvHD and only two cases of chronic

GvHD of any grade have been reported, one mild and one moderate case. Since starting the study in July 2020, SAEs have been reported

in seven patients, including infections, cardiovascular events, headache, hyperkalemia and secondary graft failure, which is loss of

a previously functioning graft. None were related to treatment as determined by the investigator.

Additional data will be presented as a late-breaking

oral abstract at the 2022 Transplant and Cellular Therapy (TCT) Meetings of ASTCT and CIBMTR to be held April 23-26, 2022.

JSP191

for Severe Combined Immunodeficiency (SCID)

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. The incidence of SCID is estimated at one in 80,000 live births across all ethnic groups. Due to the toxicities associated

with the chemotherapy regimens used in standard allogeneic hematopoietic cell transplantation (“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 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 receive busulfan (a

DNA damaging drug) as infants, they experience chronic complications such as growth retardation, cognitive defects, craniofacial abnormalities,

liver toxicity, seizure, endocrine defects including infertility and increased cancer risk.

Pre-clinical

Data for JSP191 for Severe Combined Immunodeficiency

The

ability of JSP191 to deplete human hematopoiesis was evaluated in humanized immune deficient mice that were stably engrafted with human

hematopoietic grafts at Stanford by Aaron Logan, M.D., Ph.D., et al. The mice were treated with a single dose of either 0.5 or 3.0 mg/kg

JSP191. No significant differences in depletion of human cells and HSCs after six weeks of treatment were noted between the two dose

levels of JSP191. After a single treatment with JSP191, mice were depleted of human cells in peripheral blood and bone marrow. Human

HSCs and progenitor cells (CD45+CD34+CD117+) in the bone marrow were substantially decreased for six weeks after treatment with JSP191.

To

model human transplantation with a JSP191-based conditioning regimen, humanized immune deficient mice that had been stably engrafted

with human hematopoietic cells underwent a second transplant using conditioning with JSP191 with or without the addition of an anti-CD52

antibody (Campath) that depletes human lymphocytes. The second human HSC graft was from a different donor, hence was allogeneic to the

first human graft. This second donor graft was transduced with a lentiviral vector to express the marker green fluorescence protein (“GFP”)

to allow assessment of its engraftment. CD34+ GFP marked cells were injected into untreated control mice or mice that had been treated

23 – 25 days previously with JSP191 with or without anti-CD52. After six weeks, the blood of these secondarily transplanted mice

was evaluated for evidence of GFP-marked second donor cells.

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Figure

6: JSP191 in addition to an anti-CD52 antibody demonstrated the highest level of engraftment. Engraftment was demonstrated by human CD45+

cells marked to express GFP.

Mice

pre-treated with JSP191 and anti-CD52 demonstrated the highest level of engraftment, with 67% (six of nine) of human CD45+ cells also

expressing GFP. In mice treated only with JSP191, 43% (three of seven) were GFP positive. In control mice pre-treated with anti-CD52

alone, no mice (zero of seven) showed GFP expression, while one of ten (10%) control mice not given any pre-treatment showed GFP expression

(Figure 6).

We

believe that this study can serve as a preclinical proof of concept of JSP191 conditioning enhanced engraftment with CD34+ progenitor

cells in mice, suggesting it may be efficacious in an analogous clinical setting. JSP191 appeared to be particularly effective in this

setting when used along with an anti-CD52 antibody, which was used a separate lymphodepleting agent to suppress rejection by the immune

competent first allograft.

Clinical

Data for JSP191 for Severe Combined Immunodeficiency

We have an ongoing Phase 1/2 dose escalation open

label clinical trial to evaluate JSP191 as the sole conditioning agent to achieve HSC engraftment in patients undergoing transplant for

SCID. The primary endpoint in Phase 1 is to assess the safety and tolerability of JSP191 as a conditioning agent in SCID patients. The

two primary efficacy endpoints in Phase 2 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 JSP191. Patients receive a single IV infusion of JSP191 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.

Other

studies of SCID patients have shown functional T and B cell reconstitution in patients achieving long-term myeloid donor chimerism of

at least 3%. 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.

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We believe JSP191 has enabled immune reconstitution for patients based

on naïve CD4+ T-cell levels and has shown clinical benefit in SCID patients in a re-transplant and first 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, 2021 in this open label clinical trial, fifteen re-transplant patients and three first transplant patients have been

treated in the ongoing SCID Phase 1/2 study. Most of the transplanted patients have shown engraftment of donor cells and production of

functional immune cells over up to three years of follow up (Figure 7). No JSP191 treatment related SAEs have been reported through December

31, 2021 in this clinical trial. Since starting the study in March 2017, SAEs in seven patients have been reported, including fever, infections

and hypocalcemia. None were related to treatment as determined by the investigator. Based on initial efficacy and safety results, we opened

the clinical trial to a cohort of newly diagnosed infants undergoing stem cell transplant.

We expect to complete enrollment in the Phase 1/2 clinical trial by

mid-2023.

Figure

7: Naïve CD4 T cell production post-transplant was monitored over time in (A) a matched cohort of patients receiving no conditioning

and (B) patients receiving JSP191 single agent conditioning. JSP191 conditioning in SCID patients demonstrated durable naïve T cell

production and T cell levels consistent with immune reconstitution in five out of the first six patients by two years post-transplant.

JSP191 as a Primary Therapeutic for Proliferative Disorders of

the Stem Cell

A transforming event in hematopoietic stem cells

can produce several different malignancies. Cancer stem cells possess qualities of self-renewal, prolonged survival, and the ability

to give rise to cells with more differentiated characteristics. The idea that cancer is primarily driven by a smaller population of stem

cells has important implications. For instance, many chemotherapies can shrink tumors or deplete downstream differentiated cells, but

if the therapies do not kill cancer stem cells, the tumor will grow back.

It has been shown that HSCs are the disease-initiating

cells in cancers like MDS, and that these pathogenic MDS HSCs outcompete normal HSCs present in the bone marrow of affected patients.

Furthermore, these disease-initiating HSCs express CD117, and anti-CD117 antibodies can target and eradicate these pathogenic cells.

This is especially significant in a disease like MDS where available therapies either lack disease-modifying activity or possess off-target

toxicity, preventing their use in older and/or fragile individuals who comprise most of the patients affected by MDS. Development of

anti-CD117 monoclonal antibodies, which might be safely used for targeting MDS clones, would represent a major step forward for this

disease.

We plan to evaluate JSP191 as a therapeutic for

certain MDS patients. The Revised International Prognostic Scoring System (“IPSS-R”) is a clinical assessment tool used to

evaluate risk and prognosis of newly diagnosed patients. Patients with IPSS-R scores of low or very low are not typically referred to

stem cell transplant due to the risk of transplant-related toxicities from current conditioning regiments, infection and GvHD outweighing

the patient’s expected survival with drug therapies. These patients typically suffer from anemia, thrombocytopenia or neutropenia

and are given drug therapies such as an erythropoiesis stimulating agent (“ESA”) to stimulate production of new cells to

correct their blood deficiency. However, these agents do not target the diseased hematopoietic stem cell and patients who become refractory

to ESA are dependent on routine blood transfusions, which is associated with poor survival. ESA refractory low or very low risk MDS patients

have few treatment options and are a clinical unmet need.

JSP191 and other anti-CD117 monoclonal antibodies

have been shown to deplete normal and diseased MDS human hematopoietic stem cells in clinical and pre-clinical studies. In studies in

non-human primates and healthy volunteers, administration of a single dose of JSP191 resulted in depletion of healthy hematopoietic stem

cells followed by recovery in approximately six weeks. Dr. Wendy Pang demonstrated at Stanford that our anti-CD117 monoclonal antibody

called JSP191 is capable of depleting MDS HSCs in vivo in a xenografted mouse model. New data from our MDS/AML trial of JSP191 as a conditioning

agent have revealed that the antibody can have a direct depletion effect on CD34+CD45-CD117+ cells prior to administration of fludarabine

or radiation. By depleting diseased and healthy hematopoietic stem cells, we believe that JSP191 may allow for preferential recovery

of healthy hematopoietic stem cells and restoration of normal hematopoiesis.

We intend to study JSP191 monotherapy in low-risk

MDS patients with documented cytopenia who are refractory to ESA therapy. We plan to run the primary treatment study under the existing

NDA for MDS/AML and anticipate enrollment to begin in this single arm clinical trial in early 2023.

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