What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-03-25 compared with 2024-03-19 · 156 added, 197 removed, 471 unchanged (43% of the section changed)

We are a clinical stage biopharmaceutical company.

Our strategy is to focus our efforts on the development of immune modulator product candidates with the potential to treat solid cancers, T cell lymphomas, autoimmune, allergic and infectious diseases.

We have three product candidates that are in clinical development for treatment of various solid tumors, lymphomas and autoimmune diseases.

Our lead product candidate is soquelitinib (formerly CPI-818), a selective, covalent inhibitor of ITK (interleukin 2 inducible T cell kinase) and is in a multi-center Phase 1/1b clinical trial in patients with various recurrent, malignant T cell lymphomas.

Soquelitinib is designed to inhibit the proliferation of certain malignant T cells and also to affect the differentiation of normal T cells, which could enhance immunity to tumor cells.

We believe these properties have the potential to regulate the growth and activity of both abnormal malignant T cells and abnormal T cells involved in autoimmunity and allergy.

Our second product candidate, ciforadenant, is an oral, small molecule antagonist of the A2A receptor for adenosine designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of immunosuppressive adenosine in the tumor microenvironment to the A2A receptor.

We are collaborating with the Kidney Cancer Research Consortium to evaluate ciforadenant in an open label Phase 1b/2 clinical trial as a first line therapy for metastatic RCC in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1).

Our third product candidate is mupadolimab, a humanized monoclonal antibody that is designed to react with a specific site on CD73.

In both preclinical and in vivo studies, mupadolimab has demonstrated binding to various immune cells and the enhancement of immune responses by activating B cells.

While we believe mupadolimab has the potential to be an important new therapeutic agent with a novel mechanism of action for the treatment of a broad range of cancers and infectious diseases, we are waiting to initiate a potential Phase 2 randomized clinical trial in order to prioritize the development of our other two lead product candidates.

Angel Pharmaceuticals Co.

(“Angel Pharmaceuticals”) is continuing the development of mupadolimab in China and is enrolling patients in a Phase 1 trial with mupadolimab alone and together with pembrolizumab in patients with advanced NSCLC and head and neck cancer.

Our molecularly targeted product candidates are designed to exhibit a high degree of specificity, which we believe have the potential to provide greater safety compared to other cancer therapies and may facilitate their development either as monotherapies or in combination with other cancer therapies such as immune checkpoint inhibitors or chemotherapy.

We believe the breadth and status of our pipeline demonstrates our management team’s expertise in understanding and developing immunology focused assets as well as in identifying product candidates that can be in-licensed and further developed internally to treat many types of cancer.

We hold worldwide rights to all of our product candidates (other than in greater China).

Our diverse and versatile product candidates also have enabled us to take steps to address markets in foreign countries.

In October 2020, we announced the formation and launch of Angel Pharmaceuticals, a China-based biopharmaceutical company with a mission to bring innovative quality medicines to Chinese patients for treatment of serious diseases including cancer, autoimmune diseases and infectious diseases.

We formed Angel Pharmaceuticals as a wholly owned subsidiary and it launched with a post-money valuation of approximately $106.0 million, based on an approximate $41.0 million cash investment from a Chinese investor group that includes funds associated with Tigermed and Betta Pharmaceuticals, Hisun Pharmaceuticals and Zhejiang Puissance Capital.

Such cash is not available for our use.

Contemporaneously with the financing, Angel Pharmaceuticals licensed the rights to develop and commercialize our three clinical-stage candidates – soquelitinib, ciforadenant and mupadolimab – in greater China and obtained global rights to our BTK inhibitor preclinical programs.

Under the collaboration, we currently have a 49.7% equity interest in Angel Pharmaceuticals, excluding 7% of Angel’s equity reserved for issuance under the Employee Stock Ownership Plan (“ESOP”), and are entitled to designate three individuals on Angel’s five-person board of directors.

We are a clinical stage biopharmaceutical company developing product candidates that precisely target proteins that are critical to immune cell maturation and function.

We believe our proprietary product candidates have broad potential to address cancers, immune mediated diseases and inflammatory diseases.

Our lead product candidate, soquelitinib (formerly CPI-818), is designed to bind specifically to a protein, interleukin 2 inducible T cell kinase (ITK), involved in T cell activation, T cell receptor signaling and T cell differentiation and function.

Based on the proposed mechanism of action, we believe soquelitinib has the potential to be utilized to inhibit the production of a number of inflammatory cytokines involved in diseases such as atopic dermatitis, asthma, psoriasis and fibrotic diseases.

In preclinical studies, Soquelitinib has affected T cell differentiation leading to enhanced function of T cells involved in tumor cell killing.

Since the immune cells targeted by our product candidates play a role in many diseases, our strategy is to leverage our research and development capabilities by evaluating our product candidates in clinical trials where there is an understanding of the role of specific T cells in the target indication and where we believe such product candidates have the broadest potential.

We believe this strategy has enabled us to move rapidly from preclinical to clinical trials in diverse disease areas, each with large unmet needs.

Soquelitinib entered a registrational, Phase 3 clinical trial for relapsed T cell lymphomas and is also being evaluated in a randomized, placebo controlled Phase 1 trial in patients with atopic dermatitis.

We have two additional product candidates which are in clinical development for the treatment of various solid tumors, also based on modulation of immune function.

Product Pipeline

Our product candidate pipeline includes the following:

Our product candidate pipeline and anticipated milestones include the following:

Soquelitinib (CPI-818), ITK Inhibitor.

2 unchanged sentences

T cell lymphomas are malignancies of T cells that proliferate and spread throughout the body.

These lymphomas often have tonic signaling through the T cell receptor pathway, which involves ITK.

Inhibition of ITK could result in blockade of this signaling pathway and control the growth of the malignancy.

These lymphomas often have uncontrolled tonic signaling through the T cell receptor pathway, which involves ITK.

Inhibition of ITK with soquelitinib could result in blockade of this signaling

pathway and control the growth of the malignancy.

In addition, one of the key survival mechanisms of both lymphomas and solid tumors is believed to be the reprogramming of normal T cells to create an environment in the tissues that inhibits an anti-tumor immune response and favors tumor growth.

We believe highly selective inhibitors of this enzyme will facilitate induction of normal T cell anti-tumor immunity and may be useful in the treatment of solid tumors as well as lymphomas.

Selective inhibition of ITK can block the production and function of Th2 cells, potentially leading to a biasing toward the differentiation of naïve T cells into Th1 cells, a process known as Th1 skewing.

Th1 cells lead to the generation of killer T cells that can eliminate tumor cells or viral infected cells.

Th1 cells produce interferon gamma and tumor necrosis factor that are cytokines known to destroy cancer cells.

We believe that soquelitinib can lead to reprograming of normal immune responses that also could be beneficial for the treatment of certain autoimmune and allergic diseases.

Overactive Th2 cells play a role in autoimmune and allergic diseases, which can potentially be ameliorated by selective ITK inhibition by blocking Th2 function and their production of inflammatory cytokines.

T cell signaling involving ITK is required in the development of many T cell lymphomas.

The ITK cell signaling pathway is similar to the signaling that occurs in B cells, which is mediated by a homologous enzyme known as BTK, the target of ibrutinib, an approved treatment for patients with B cell lymphomas and leukemias.

ITK is expressed in many T cell lymphomas, including peripheral T cell lymphoma (“PTCL”), angioimmunoblastic T cell lymphoma (“AITL”), cutaneous T cell lymphomas (“CTCL”), anaplastic large cell lymphomas (“ALCL”), natural killer T cell lymphomas (“NKTCL”) and other T cell malignancies.

In ITK genetic knockout mice, which completely lack expression of ITK, T cells exhibit defects in T helper cell differentiation and cytokine secretion but retain the ability to differentiate into cytotoxic T cells that secrete IL-2 and

interferon gamma (“IFNg”), which are the cells responsible for tumor rejection.

A normal functioning immune system maintains balance between inflammation, needed to fight infection or eliminate noxious agents, and suppression of inflammation necessary when the inflammatory signals are eliminated.

This balance is restored through the action of T regulatory cells, which dampen inflammatory responses.

ITK plays a vital role in the function of these regulatory T cells where it acts to modulate immune responses.

We believe that skewing T helper cell differentiation to favor cytotoxic T cells, known as Th1 skewing, may be beneficial in treating T cell lymphomas and many other types of cancer.

Mice with genetic knock-out of ITK also demonstrate a reduction in Th2 cells, which produce the cytokines that are often responsible for autoimmunity and allergy.

We have developed soquelitinib by covalently targeting the cysteine amino acid residue at position 442 in the ITK protein.

Mice with genetic knock-out of ITK also demonstrate a reduction in Th2 cells, which produce the cytokines that are often responsible for autoimmunity and allergy such as interleukin (Il) Il-4, Il-5, Il-13, Il-17 and many others.

We have designed and developed soquelitinib to covalently target the cysteine amino acid residue at position 442 in the ITK protein.

We believe this irreversible targeting of ITK has the potential to provide a potent, selective and prolonged duration of activity without the need for high systemic exposures and thereby improve the therapeutic window.

This approach was previously used by our cofounders to generate ibrutinib.

We believe that the potential selectivity of soquelitinib could mimic the immune effects seen in ITK knockout mice and skew the immune response toward a more favorable anti-tumor immune response as well as reducing the activity of Th2 cells.

The blockade of Th2 differentiation has the potential to suppress inflammatory reactions involved in various autoimmune and allergic diseases.

Soquelitinib was designed to have the necessary selectivity to specifically block ITK function without altering other closely related enzymes involved in T cell differentiation.

We believe such selectivity is required for achieving Th1 skewing and Th2 blockade, as established by ITK genetic knockout studies in mice.

ITK also plays a role in the proliferation of some T cell lymphomas and we believe its inhibition could lead to growth arrest and/or tumor cell cytotoxicity.

In our preclinical studies of soquelitinib, objective tumor responses were observed in dogs with spontaneous T cell lymphomas.

Soquelitinib is orally bioavailable and has achieved cellular occupancy of the target in vivo in various animal models.

Pre-clinical studies have demonstrated that soquelitinib was well-tolerated in vivo and resulted in inhibition of T cell activation and differentiation.

Soquelitinib is currently being studied in a Phase 1/1b clinical trial that was designed to select the optimal dose of soquelitinib and evaluate its safety, pharmacokinetics (“PK”), target occupancy, immunologic effects, biomarkers and efficacy.

The study employs an adaptive, expansion cohort design, with an initial phase that evaluated escalating doses (100, 200, 400 or 600 mg taken twice a day) in successive cohorts of patients, followed by a second phase that is designed to evaluate safety and tumor response to the recommended dose of soquelitinib in disease-specific patient cohorts.

Selective inhibition of ITK can block the production and function of Th2 and Th17 helper T cells, potentially leading to a biasing toward the differentiation of naïve T cells into Th1 helper T cells, a process known as Th1 skewing.

Th1 cells lead to the generation of killer T cells that can eliminate tumor cells or viral infected cells.

Th1 cells produce interferon gamma and tumor necrosis factor that are cytokines known to destroy cancer cells.

We believe, based on our preclinical and Phase 1/1b data from our T cell lymphoma clinical trial, that soquelitinib has the potential to reprogram normal immune responses that also could be beneficial for the treatment of certain autoimmune, inflammatory and allergic diseases.

Overactive Th2 and Th17 cells are known to play a role in autoimmune, inflammatory and allergic diseases, which can potentially be ameliorated by selective ITK inhibition by blocking Th2 and Th17 function and their production of inflammatory cytokines such as IL4, IL5, IL13, IL17 and others.

Soquelitinib for treatment of T cell lymphomas.

Soquelitinib is currently being studied both in cancer and in immune mediated disease.

A Phase 1/1b clinical trial was conducted in patients with relapsed T cell lymphomas that was designed to select the optimal dose of soquelitinib and evaluate its safety, pharmacokinetics (“PK”), target occupancy, immunologic effects, biomarkers and efficacy.

The study is no longer enrolling new patients, however, some of the patients remain on therapy and are continuing to receive follow-up monitoring.

The study employs an adaptive, expansion cohort design, with an initial phase that evaluated escalating doses (100, 200, 400 or 600 mg taken twice a day) in successive cohorts of patients, followed by a second phase that was designed to evaluate safety and tumor response to the recommended dose of soquelitinib in disease-specific patient cohorts.

The study has enrolled patients from the United States, Australia, China and South Korea with several types of advanced, refractory T cell lymphomas.

No dose limiting toxicities were observed in any of the dose levels.

As of January 22, 2024, and in a safety population of 73 patients, no hematologic, renal or hepatic treatment-related adverse events were observed and the most common grade 3 to 4 adverse event was pruritus, seen in four patients with lymphoma involving skin.

As of November 27, 2024, and in a safety population of 75 patients, no hematologic, renal or hepatic treatment-related adverse events were observed and the most common grade 3 to 4 adverse event was pruritus, seen in four patients with lymphoma involving skin.

The optimum dose was determined to be 200 mg twice per day based on anti-tumor efficacy and pharmacodynamic studies which revealed full occupancy of the ITK active site by the drug.

This dose was also consistent with dose-response effects seen in preclinical experiments both in vitro and in vivo.

Soquelitinib is designed to induce a host anti-tumor cell mediated immune response that requires normal functioning T cells and an adequately functioning immune system.

Therapies for T cell lymphomas, such as chemotherapy, are frequently immunosuppressive.

Data from the Phase 1/1b clinical trial suggest that the number of prior therapies and immunocompetence were associated with tumor response to soquelitinib and are important patient eligibility requirements, with an optimum range of ≥1 to ≤3 prior therapies.

Interim data from the Phase 1/1b clinical trial were presented at the American Society of Hematology Annual Meeting (“ASH”) in December 2023.

At that time, we also announced interim data from the trial as of November 21, 2023 on 21 evaluable patients receiving a dose of 200 mg twice per day and revealed an objective response rate (“ORR”) of 33.3% with 3 complete responses (“CRs”) and 4 partial responses (“PRs”).

Since that report, one of the patients achieving a PR continued to respond and showed a CR resulting in an ORR of 33.3% with 4 CRs and 3 PRs as of an updated cutoff date of January 22, 2024.

As of January 22, 2024 (as shown below in Figures 1-3), a total of 23 patients were enrolled in the Phase 1/1b trial at the 200 mg two-times a day dose, including 21 evaluable patients with ≥1 and ≤3 prior therapies.

Several additional patients experiencing tumor regression were continuing on therapy as of the data cutoff.

Waterfall Plot for Patients Receiving 200 mg Dose Twice per Day of Soquelitinib in the Phase 1/1b Clinical Trial for Peripheral T Cell Lymphoma.

The plot shows the best percent change in tumor volume in the 21 evaluable patients, as of January 22, 2024, that were measurable by CT scan or by Modified Severity-Weighted Assessment Tool (mSWAT) for patients with cutaneous involvement.

Swimmer Plot Demonstrating Response and Time on Therapy.

Tumor histologies as of January 22, 2024 are also shown indicating different types of T cell lymphoma.

PTCL-NOS, peripheral T cell lymphoma not otherwise specified;

CTCL, cutaneous T cell lymphoma of either Sezary or mycosis fundoides type;

NKTCL, natural killer cell T cell lymphoma;

ALCL, anaplastic large cell lymphoma;

AITL, angioimmunoblastic T cell lymphoma.

Table Comparing Soquelitinib Data from Phase 1 to Data Reported for Standard of Care Agents, Pralatrexate and Belinostat.

Belinostat and pralatrexate received accelerated approval for relapsed PTCL and will be utilized in the standard of care arm of the planned soquelitinib Phase 3 registration trial.

Patient characteristics such as age, number of prior therapies and response to most recent prior therapies are similar to those reported for belinostat and pralatrexate.

Progression-free survival (“PFS”) is the primary endpoint for the planned Phase 3 clinical trial;

ORR, overall survival (“OS”) and duration of response are secondary endpoints.

The ORR, disease control rate, PFS and OS presented below were not derived from a head-to-head study and are for informational purposes only.

Differences exist between trial designs, subject characteristics and other factors, and caution should be exercised when comparing data across unrelated studies.

Data presented for soquelitinib is as of January 22, 2024.

Soquelitinib Induced Th1 Skewing and Th2 Blockade .

The figures below show that the results in patients, as of December 22, 2022, with tissue sampling support the role in therapy of cancer and immune diseases.

In August 2023, we completed an End-of-Phase/Pre-Phase 3 meeting with the Food and Drug Administration (“FDA”) regarding our plans to conduct a potentially registrational Phase 3 clinical trial of soquelitinib in relapsed PTCL.

At that time, we also announced interim data from the trial as of November 21, 2023 on 21 evaluable patients receiving a dose of 200 mg twice per day (“200 mg BID”) and revealed an objective response rate (“ORR”) of 33.3% with 3 complete responses (“CRs”) and 4 partial responses (“PRs”).

As of July 16, 2024, 25 patients (≤ 3 prior therapies) were enrolled in the trial at the 200 mg BID dose,

including 23 evaluable patients.

For the 23 evaluable patients, objective responses (CR plus PR) were seen in nine patients (39%), including six CRs (26%) and three PRs.

The median progression free survival was 6.2 months.

As of November 27, 2024, four of the responding patients remained on therapy;

3 with CRs and one with a PR.

The FDA provided feedback on our proposed registration trial, including the proposed endpoints.

We anticipate that we will be able to initiate this clinical trial in the third quarter of 2024.

We initiated this clinical trial in the third quarter of 2024.

The clinical trial is designed to enroll a total of 150 patients with relapsed PTCL that have received ≥ 1 prior therapy and≤3 prior therapies.

The number of prior therapies in this range selects for immunocompetent patients.

Patients will be randomized 1:1 to soquelitinib 200 mg two-times a day or one of the standard of care chemotherapies.

The standard of care agent will be based on the physician’s choice of either belinostat or pralatrexate.

The primary endpoint will be progression-free survival.

Secondary endpoints will include objective response rate, overall survival and duration of response.

We are recruiting investigators and anticipate that leading academic and private medical centers with significant experience in lymphoma research will participate in the trial, including investigators who have conducted other Phase 3 clinical trials in T cell lymphoma and authored many peer-reviewed articles on lymphomas.

Patients are being randomized 1:1 to soquelitinib 200 mg two-times a day or one of the standard of care chemotherapies.

The standard of care agent is selected based on the physician’s choice of either belinostat or pralatrexate.

The primary endpoint is progression-free survival.

Secondary endpoints include objective response rate, overall survival and duration of response.

Leading academic and private medical centers with significant experience in lymphoma research are participating in the trial, including investigators who have conducted other Phase 3 clinical trials in T cell lymphoma and authored many peer-reviewed articles on lymphomas.

There are currently no FDA fully approved agents for the treatment of relapsed PTCL.

In July 2024, soquelitinib received Fast Track designation for treatment of adult patients with relapsed or refractory peripheral T cell lymphoma after at least 2 lines of systemic therapy.

As reported at the International Conference of Malignant Lymphoma in June 2023, preclinical data suggest that ITK inhibition with soquelitinib has the potential to treat solid and hematological cancers based on its novel proposed mechanism of action.

12 unchanged sentences

We are planning a Phase 1b/2 clinical trial, in collaboration with the Kidney Cancer Research Consortium, of soquelitinib in solid tumors in patients with renal cell cancer who have failed checkpoint inhibitor therapy.

In July 2023, we announced the posting of preclinical data on soquelitinib in bioRxiv, the online archive for unpublished preprints in the life sciences, which highlighted the potential of selective inhibition of ITK to enhance anti-tumor immune response to hematologic and solid tumors and provide a novel approach to cancer immunotherapy.

Key results from the preclinical studies described in the paper demonstrated that soquelitinib:

In December 2024, we and our academic collaborators published results describing the chemistry, enzymology and preclinical anti-tumor activity of soquelitinib in the journal npj Drug Discovery.

Key results from the publication include that soquelitinib:

● Selectively bound to and inhibited ITK function while sparing other closely related kinases, including resting lymphocyte kinase.

● Inhibited Th2 T cell function and the production of various Th2 cytokines leading to Th1 skewing and production of interferon gamma and tumor necrosis factor, which are important cytokines in tumor rejection.

Th2 cytokines have been previously implicated in promoting tumor growth and are also involved in

autoimmune and allergic diseases.

Th2 cytokines have been previously implicated in promoting tumor growth and are also involved in autoimmune and allergic diseases.

● Activated cytotoxic killer cells and increases infiltration of these cells into tumors.

2 unchanged sentences

● Led to in vivo anti-tumor activity in several mouse tumor models, including colon, renal, melanoma, B cell and T cell tumor.

In September 2023, a paper was published by an independent academic group in Scientific Reports supporting the potential of ITK inhibition for treatment of solid tumors.

The preclinical data demonstrated a reduction and reversal of T cell exhaustion markers and an increase in the infiltration of killer T cells into tumors, consistent with soquelitinib’s proposed mechanism of action.

The paper highlights the potential of selective ITK inhibition for the treatment of cancers and helps to confirm preclinical and clinical results generated by Corvus.

In November 2023, we announced the posting of preclinical data on soquelitinib in bioRxiv that demonstrated that ITK’s selective inhibition produced therapeutic benefits in several autoimmune and allergy preclinical models, including psoriasis, asthma, pulmonary fibrosis, scleroderma and graft versus host disease.

1 unchanged sentence

The novel mechanism is a result of ITK inhibition and blockade of formation of Th2 and Th17 cells.

Soquelitinib is Active in Imuniquimod Psoriasis Model.

Improved histology, and reduction of Th17, IL-17 reflected in below figure.

We plan to conduct a randomized, placebo-controlled Phase 1 trial in 64 patients with moderate to severe atopic dermatitis that have failed at least one prior therapy.

The trial design will evaluate four different 28-day dosing regimens of soquelitinib compared to a placebo group.

The endpoints include safety and improvement in eczema area and severity score (“EASI”).

Patients and physicians will be blinded to treatment assignment.

We anticipate that this study will start in the second quarter of 2024.

The FDA has granted Fast Track Designation to soquelitinib for the treatment of adult patients with relapsed or refractory peripheral T cell lymphoma (PTCL) after at least two lines of systemic therapy.

In addition to Fast Track Designation, soquelitinib has also been granted FDA Orphan Drug Designation for the treatment of T cell lymphoma.

Soquelitinib for treatment of atopic dermatitis.

In April 2024, we initiated a randomized, double-blind, placebo-controlled Phase 1 clinical trial with soquelitinib in patients with moderate to severe atopic dermatitis that previously failed one prior topical or systemic therapy.

The clinical trial is planned to enroll 64 patients into one of four dosing cohorts in a 3:1 ratio (12 active and 4 placebo) to receive either soquelitinib or placebo.

The cohorts are sequentially enrolled and will examine 100 mg oral twice per day, 200 mg oral once per day, 200 mg oral twice per day and 400 mg oral once per day.

Patients are treated for 28 days and are then followed for an additional 30 days with no therapy.

The primary endpoints include safety and tolerability, and efficacy, measured by improvement in Eczema Area and Severity Index (“EASI”) score, Investigator Global Assessment (“IGA”), reduction in itch and various cytokine biomarkers.

EASI scores are also evaluated by the percent of patients that achieve a specified percent reduction in EASI score – EASI 50 for patients that achieved a 50% reduction;

EASI 75 for a 75% reduction;

and EASI 90 for a 90% reduction.

Corvus and a data monitoring committee will be able to monitor the data from the trial as the trial progresses.

On January 13, 2025, we reported top-line results from 16 patients in Cohort 1 (12 patients in the soquelitinib group receiving 100 mg orally twice per day vs.

four receiving placebo) and 10 patients in Cohort 2 (seven patients in the soquelitinib group receiving 200 mg orally once per day vs.

three receiving placebo) for which 28 days of treatment had been completed.

For those 19 patients in the soquelitinib group, 26% achieved IGA 0 or 1 and 37% achieved EASI 75;

and of the seven in the placebo group, none achieved IGA 0 or 1 or EASI 75.

No significant safety issues were observed and no clinically significant laboratory abnormalities were seen.

All 10 patients from Cohort 2 completed 28 days of dosing at the full dose of 200 mg orally once per day.

Cohort 2 of the trial is fully enrolled (N=16) and we are nearing completion of enrollment in the third cohort.

We plan to report topline results from Cohorts 1, 2 and 3 in May 2025.

To date, over 100 patients have been treated with soquelitinib on our lymphoma and atopic dermatitis clinical trials.

Some of the lymphoma patients received continuous therapy for up to two years.

Beyond our current and planned clinical trials for soquelitinib, we also continue to advance our next-generation ITK inhibitor preclinical product candidates, which were designed to deliver precise T-cell modulation that is optimized for specific immunology indications.

The next-generation ITK inhibitor candidates are part of our ongoing business development efforts to maximize the potential of our ITK inhibitor programs and other programs.

We have issued patents covering composition of matter and uses of our ITK inhibitors and hold exclusive worldwide rights (except for greater China) for all indications.

Ciforadenant Adenosine A2A Receptor Antagonist.

Our second product candidate, ciforadenant, is an oral, small molecule antagonist of the A2A receptor for adenosine designed to disable a tumor’s ability to subvert attack by the

immune system by blocking the binding of immunosuppressive adenosine in the tumor microenvironment to the A2A receptor.

We are collaborating with the Kidney Cancer Research Consortium to evaluate ciforadenant in an open label Phase 1b/2 clinical trial as a first line therapy for metastatic renal cell cancer (“RCC”) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1).

The clinical trial is expected to enroll up to 60 patients and interim data are anticipated in 2024.

This study has fully enrolled patients in the Phase 1b safety portion of the trial and is now enrolling patients in the Phase 2 portion of the trial.

The safety portion of the study evaluated the safety of ciforadenant administered in combination with nivolumab and ipilimumab.

Ciforadenant preclinical data were presented at the Japanese Cancer Association and American Association for Cancer Research Precision Cancer Medicine International Conference, which took place June 28 to June 30, 2023 in Kyoto, Japan.

The presentation highlighted data supporting the synergy between ciforadenant and immune checkpoint blockade (“ICB”), leading to a proinflammatory response.

Highlights of the presentation included:

● Depletion of myeloid cells abolished the synergy of ciforadenant and ICB in a murine melanoma model.

● The combination of ciforadenant with ICB upregulated the genes involved in the IL-12/STAT4 signaling axis, which led to the development of CXCR3+ IFNγ-producing Th1 helper cells.

● Ciforadenant treatment increased production of chemokine CXCL10, a ligand for recruitment of CXCR3+ Th1 helper cells into the tumor.

● Ciforadenant modulated antitumor responses by turning the tumor microenvironment into the proinflammatory state.

● The combination of ciforadenant with ICB promoted the production of several proinflammatory cytokines such as IL-6, TNFa, and IFNg.

In 2018, we published preclinical findings in animal tumor models demonstrating that treatment with anti-CTLA4 antibody combined with ciforadenant provided synergistic anti-tumor activity based on a novel proposed mechanism of action.

The efficacy endpoints for the trial are deep response rate, defined as CR plus PRs of greater than 50% tumor volume reduction as well as progression free survival.

The clinical trial is planned to enroll up to 60 patients.

The protocol defined pre-specified statistical threshold for efficacy is a 50% increase above the 32% deep response rate seen with previous ipilimumab/nivolumab combination trials in RCC conducted by investigators at the Kidney Cancer Research Consortium.

An interim analysis performed on May 31, 2024 of the clinical trial has met the interim threshold for efficacy and therefore enrollment continued.

Enrollment in the clinical trial now has been completed and patients are being followed.

Mupadolimab, B Cell Activating Anti-CD73 Antibody.

2 unchanged sentences

Angel Pharmaceuticals is continuing the development of mupadolimab in China and is enrolling patients in a Phase 1 trial with mupadolimab alone and together with pembrolizumab in patients with advanced NSCLC and head and neck cancer.

CPI-182, Anti-CXCR2 Antibody Designed to Block Inflammation and Myeloid Suppression.

In 2017, we in-licensed this monoclonal antibody designed to block CXCR2, a novel target expressed on neutrophils and various inflammatory cells including myeloid derived suppressor cells (“MDSC”).

Preclinical studies have demonstrated that this antibody blocked neutrophil function and migration, and MDSCs.

MDSCs are involved in tumor immunosuppression and blockade of these cells may improve anti-tumor immunity.

A publication describing this antibody was published in the journal MABS in January 2021.

Preclinical data in vivo in mice demonstrated that CPI-182 was active in models of rheumatoid arthritis and in models of atopic dermatitis.

We believe these data support the role of CXCR in inflammatory diseases and demonstrate that CPI-182 may have the potential to treat these conditions.

This product candidate is now in Investigational New Drug application (“IND”)-enabling studies.

CPI-935, Adenosine A2B Receptor Antagonist.

Adenosine A2B receptors have been found to play an important role in the immune response to tumors as well as in inflammation and fibrosis.

Similar to adenosine A2A receptors, adenosine binds to adenosine A2B receptors, which leads to immunosuppression.

Preclinical models have shown that inhibition of A2B receptors prevented fibrosis.

In 2018, we selected a development candidate for this program, a small molecule antagonist of the A2B receptor.

Angel Pharmaceuticals is continuing the development of mupadolimab in China.

Manufacturing

We do not own or operate, and currently have no plans to establish any manufacturing facilities.

We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates for clinical testing, as

well as for manufacture of any products that we may commercialize.

We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates for clinical testing, as well as for manufacture of any products that we may commercialize.

We are able to internally produce small quantities of our product candidates required for relatively short preclinical animal studies.

6 unchanged sentences

We believe that the development experience of our scientific and management teams, as well as the strength and promise of our product candidates, provides us with a competitive advantage;

nevertheless, we face potential competition from myriad sources, including pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions.

Kyowa Hakko Kirin has approval in Japan and the United States for istradefylline, an A2A antagonist, in Parkinson’s disease.

Within oncology, Novartis has announced an exclusive licensing agreement with Palobiofarma SL and is conducting a Phase 1 trial with an A2A antagonist.

AstraZeneca plc is conducting clinical trials with an A2A antagonist for use in cancer therapy.

Merck KgaA has entered into a pre-clinical collaboration with Domain Therapeutics Inc.

to develop programs targeting the adenosine pathway.

In addition, Redoxtherapies, which was acquired by Juno Therapeutics and subsequently by Celgene, and Arcus Biosciences are developing A2A receptor antagonists for cancer.

Astra Zeneca, Bristol-Myers Squib, and Novartis, in partnership with Surface Oncology, have initiated clinical trials with anti-CD73 antibodies in cancer patients.

Recently, Astra Zeneca reported positive results in a Phase 2 clinical trial in Stage 3 NSCLC with the combination of durvalumab and their anti CD73 antibody, oleclumab.

More generally, in the field of immuno-oncology, there are large pharmaceutical companies with approved products or products in late-stage development that target other immune checkpoints, including PD-1, PD-L1 or CTLA-4.

These companies include Bristol-Myers Squibb (nivolumab, ipilimumab), Merck (pembrolizumab), Genentech (atezolizumab) and AstraZeneca (durvalumab, tremelimumab).

Janssen Pharmaceuticals and AbbVie are co-marketing Imbruvica (ibrutinib), which is a small molecule inhibitor of the kinase BTK that has also been reported to inhibit ITK.

nevertheless, we face

potential competition from myriad sources, including pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions.

Soquelitinib is an investigational oral therapy in development for the treatment of immune diseases and cancer.

Soquelitinib is designed to precisely inhibit ITK, a critical signaling pathway in the immune system, and is currently in Phase 3 for relapsed and refractory PTCL (R/R PTCL) as well as Phase 1 for atopic dermatitis (AD).

If approved for use in patients with AD, we will potentially face branded competition from dupilumab, a biologic approved in 2017, as well as biologics tralokinumab, nemolizumab, and lebrikizumab.

In addition, there are several companies developing treatments that may be approved for AD including large pharmaceutical and biotechnology companies such as Pfizer, Sanofi, Amgen, GSK, Lilly, AbbVie, and Incyte.

Currently approved treatments for R/R PTCL include belinostat and pralatrexate, both under accelerated approval.

In addition, brentuximab vedotin (BV), is approved for CD30-positive PTCL patients, including front line as well as a subset of previously treated patients.

There are also several companies developing treatments for PTCL including, but not limited to, valemetostat (approved in Japan), duvelisib, linperlisib, and golidocitinib (approved in China).

Ciforadenant is an investigational A2A receptor antagonist intended to treat solid tumors.

Arcus Biosciences is developing an A2A receptor antagonist for cancer.

Mupadolimab is a humanized monoclonal antibody designed to react with a specific site on CD73 and is intended to treat solid tumors.

AstraZeneca (AZ) has reported positive results in a Phase 2 clinical trial in Stage 3 NSCLC with the combination of durvalumab and their anti CD73 antibody, oleclumab, and is currently conducting a Phase 3 trial with durvalumab and olecumab.

Many of the companies against which we may compete have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trials sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Intellectual Property

11 unchanged sentences

As of February 6, 2025, our owned and licensed patent portfolio consisted of fourteen licensed U.S.

issued patents, one licensed U.S.

pending patent applications, ten owned U.S.

issued patents, eight owned U.S.

pending patent applications, two pending Patent Cooperation Treaty (“PCT”) applications, and three owned U.S.

provisional patent applications directed to soquelitinib, ciforadenant and mupadolimab, and certain of our other proprietary technology, inventions, improvements or other potential product candidates.

In addition, our owned and licensed patent portfolio included thirty-eight licensed patents, eight licensed patent applications, thirty-eight owned patents, and twenty-six owned patent applications pending in jurisdictions outside of the United States that are foreign counterparts to one or more of the foregoing U.S.

issued patents, thirteen owned U.S.

issued patents, six owned U.S.

pending patent applications, four owned pending Patent Cooperation Treaty (“PCT”) applications, and one owned U.S.

provisional patent applications directed to soquelitinib, ciforadenant and

mupadolimab, and certain of our other proprietary technology, inventions, improvements or other potential product candidates.

In addition, our owned and licensed patent portfolio included forty licensed patents, four licensed patent applications, forty-one owned patents, and thirty owned patent applications pending in jurisdictions outside of the United States that are foreign counterparts to one or more of the foregoing U.S.

patents and patent applications.

7 unchanged sentences

The term of patents outside of the United States varies in accordance with the laws of the foreign jurisdiction, but typically is also 20 years from the earliest effective filing date.

The issued United States patents we license from Vernalis directed to the composition of matter of ciforadenant and its method of use for treating disorders treatable by purine receptor blocking are expected to expire between September 2028 and June 2029, excluding any patent term extension that may be available.

The issued United States patents we license from Vernalis directed to the composition of matter of ciforadenant and its method of use for treating disorders treatable by purine receptor blocking are expected to expire around June 2029, excluding any patent term extension that may be available.

The granted U.S.

and foreign patents, pending U.S.

and foreign patent applications, and PCT International patent application, if granted as patents, that we own directed to the methods of treatment for ciforadenant are expected to expire between December 2036 and December 2043, excluding any patent term extension that may be available.

and foreign patent applications, and PCT International patent application, if granted as patents, that we own directed to the methods of treatment for ciforadenant are expected to expire between December 2036 and April 2045, excluding any patent term extension that may be available.

The granted U.S.

10 unchanged sentences

In particular, our ability to stop third parties from making, using, selling, offering to sell, or importing products that infringe our intellectual property will depend in part on our success in obtaining and enforcing patent claims that cover our technology, inventions, and improvements.

With respect to both licensed and company-owned intellectual property, we cannot guarantee that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications we may file in the future, nor can we be sure that any patents that may be granted to us in the future will be commercially useful in protecting our products, the methods of

use or manufacture of those products.

Moreover, even the issued patents that we license do not guarantee us the right to practice our technology in relation to the commercialization of our products.

1 unchanged sentence

For example, third parties may have blocking patents that could be used to prevent us from commercializing our product candidates and practicing our proprietary technology, and the issued patents that we in-license and those that may issue in the future may be challenged, invalidated, or circumvented, which could limit our ability to stop competitors from marketing related products or could limit the term of patent protection that otherwise may exist for our product candidates.

In addition, the scope of the rights granted under any issued patents may not provide us with protection or competitive advantages against competitors with similar technology.

addition, the scope of the rights granted under any issued patents may not provide us with protection or competitive advantages against competitors with similar technology.

Furthermore, our competitors may independently develop similar technologies that are outside the scope of the rights granted under any issued patents that we own or exclusively in-license.

18 unchanged sentences

The agreement will expire on a product-by-product and country-by-country basis upon the expiration of our payment obligations to Vernalis in respect of a particular product and country.

Both parties have the right to terminate

the agreement in the event of an uncured material breach by the other party.

Both parties have the right to terminate the agreement in the event of an uncured material breach by the other party.

We may also terminate the agreement at our convenience by providing 90 days written notice, provided that we have not received notice of our own default under the agreement at the time we exercise such termination right.

35 unchanged sentences

The process required by the FDA before a drug or biologic may be marketed in the United States generally involves the following:

● completion of preclinical laboratory tests, animal studies and formulation studies in accordance with Good Laboratory Practice (“GLP”) regulations and other applicable regulations;

● completion of certain preclinical laboratory tests, animal studies and formulation studies in accordance with Good Laboratory Practice (“GLP”) regulations and other applicable regulations;

● submission to the FDA of an IND, which must become effective before human clinical trials may begin;

1 unchanged sentence

● performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice (“GCP”) regulations to establish the safety and efficacy of the proposed drug, or safety, purity and potency of the proposed biologic for its intended use;

● submission to the FDA of an NDA or BLA after completion of all clinical trials ;

● submission to the FDA of an NDA or BLA;

● s atisfactory completion of an FDA Advisory Committee review, if applicable;

● a determination by the FDA within 60 days of its receipt of an NDA or BLA to file the application for review;

● satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with current Good Manufacturing Practice (“cGMP”) requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity , and of selected clinical investigation sites to assess compliance with GCP ;

● satisfaction of selected clinical investigation sites to assess compliance with GCP ;

● FDA review and approval of the NDA or BLA to permit commercial marketing of the product for particular indications for use in the United States .

21 unchanged sentences

Post-approval trials, sometimes referred to as Phase 4 studies, may be conducted after initial marketing approval.

These trials are used to gain additional experience from the treatment of patients in the intended therapeutic

These trials are used to gain additional experience from the treatment of patients in the approved therapeutic indication.

In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA or BLA.

14 unchanged sentences

a waiver of such fees may be obtained under certain limited circumstances.

In addition, the Pediatric Research Equity Act (“PREA”), which requires a sponsor to conduct pediatric clinical trials for most drugs and biologics, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration.

Under PREA, original NDAs, BLAs and supplements thereto must contain a pediatric assessment unless the sponsor has received a deferral or waiver.

The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is deemed to be safe and effective.

The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations.

A deferral may be granted for several reasons, including a finding that the drug or biologic is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin.

The FDA must send a non compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

Within 60 days following submission of the application, the FDA reviews all NDAs and BLAs submitted to ensure that they are sufficiently complete for substantive review before it accepts them for filing.

4 unchanged sentences

The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP compliant to assure and preserve the product’s identity, strength, quality and purity.

The FDA reviews a BLA to determine, among other things whether the product is safe, pure and potent and the facility in which it is manufactured, processed, packed or held meets standards designed to assure the product’s continued safety, purity and potency.

The FDA reviews a BLA to determine, among other things whether the product is safe, pure and potent and the facility in which it

is manufactured, processed, packed or held meets standards designed to assure the product’s continued safety, purity and potency.

Under the Prescription Drug User Fee Act guidelines that are currently in effect, the FDA has a goal to complete a standard review of an NDA for a new molecular entity or an original BLA within ten months after the filing date, or, if the application qualifies for priority review, within six months after the filing date.

Before approving an NDA or BLA, the FDA will inspect the facility or facilities where the product is manufactured.

1 unchanged sentence

The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.

After the FDA evaluates an NDA or BLA, it will issue an approval letter or a Complete Response Letter.

After the FDA evaluates an NDA or BLA and conducts any required inspections, it will issue an approval letter or a Complete Response Letter.

An approval letter authorizes commercial marketing of the drug with prescribing information for specific indications.

A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be

approved in its present form.

A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be approved in its present form.

A Complete Response Letter usually describes the specific deficiencies in the NDA or BLA identified by the FDA and may require additional clinical data, such as an additional clinical trial or other significant and time consuming requirements related to clinical trials, nonclinical studies or manufacturing.

8 unchanged sentences

Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.

Under PREA, original NDAs, BLAs and supplements thereto must contain a pediatric assessment unless the sponsor has received a deferral or waiver.

The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations.

The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

Orphan Drug Designation

24 unchanged sentences

A product receiving accelerated approval may be subjected to expedited withdrawal procedures if the sponsor fails to conduct any required confirmatory trials in a timely manner, or if such trials fail to verify the predicted clinical benefit.

In addition, the FDA currently requires as a condition for accelerated approval pre approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

In addition, the FDA requires as a condition for accelerated approval pre approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

Fast Track designation, Breakthrough Therapy designation, priority review and accelerated approval do not change the standards for approval but may expedite the development or approval process.

35 unchanged sentences

The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products.

At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law.

Government Regulation Outside of the United States

37 unchanged sentences

(i) medicinal products derived from biotechnological processes, such as genetic engineering, (ii) medicinal products that contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative or autoimmune diseases and other immune dysfunctions and viral diseases, (iii) designated orphan medicines and (iv) advanced therapy medicinal products (“ATMPs”), such as gene therapy, somatic cell therapy or tissue-engineered medicines.

The centralized procedure may at the request of the applicant also be used in certain other

cases and in particular for any other products containing new active substances not authorized in the EU or for product candidates which constitute a significant therapeutic, scientific, or technical innovation or for which the granting of authorization would be in the interests of public health in the EU.

It is likely that the centralized procedure would apply to the product candidates we are developing.

The centralized procedure may at the request of the applicant also be used in certain other cases and in particular for any other products containing new active substances not authorized in the EU or for product candidates which constitute a significant therapeutic, scientific, or technical innovation or for which the granting of authorization would be in the interests of public health in the EU.

It is likely that the centralized procedure would apply

to the product candidates we are developing.

Under the centralized procedure, the maximum timeframe for the evaluation of a MAA by the EMA is 210 days, excluding clock stops.

24 unchanged sentences

(1) it is intended for the diagnosis, prevention or treatment of a life threatening or chronically debilitating condition;

(2) either (a) such condition affects not more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the

benefits derived from the orphan status, would not generate sufficient return in the EU to justify the necessary investment;

and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.

(2) either (a) such condition affects not more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from the orphan status, would not generate sufficient return in the EU to justify the necessary investment;

by the condition.

The application for orphan designation must be submitted before the MAA.

22 unchanged sentences

The advertising and promotion of medicinal products is also subject to laws concerning promotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices.

All advertising and promotional activities for the product must be consistent with the approved summary of product characteristics, and therefore all off-label promotion is prohibited.

advertising and promotional activities for the product must be consistent with the approved summary of product characteristics, and therefore all off-label promotion is prohibited.

Direct-to-consumer advertising of prescription medicines is also prohibited in the EU.

15 unchanged sentences

A person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it to have committed a violation;

● The federal false claims laws, including the False Claims Act, which prohibit any person or entity from, among other things, knowingly presenting, or causing to be presented, a false, fictitious or fraudulent claim for payment to, or approval by, the federal government or knowingly making, using or causing to be made

or used a false record or statement material to a false or fraudulent claim to the federal government.

In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act;

In addition, the government may assert that a claim including items or services resulting from a violation of

the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act;

● The federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which prohibits, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

14 unchanged sentences

Moreover, a third-party payor’s decision to provide coverage for a pharmaceutical or biological product does not imply that an adequate reimbursement rate will be approved.

Adequate third-party

reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

In addition, coverage and reimbursement for new products can differ significantly from payor to payor.

Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

In addition, coverage and reimbursement for new products can differ

significantly from payor to payor.

One third-party payor’s decision to cover a particular medical product or service does not ensure that other payors will also provide coverage for the medical product or service, or will provide coverage at an adequate reimbursement rate.

10 unchanged sentences

extended the Medicaid Drug Rebate Program to utilization of prescriptions of individuals enrolled in Medicaid managed care plans;

imposed mandatory discounts for certain Medicare Part D beneficiaries as a condition for manufacturers’ outpatient drugs coverage under Medicare Part D;

subjected drug manufacturers to new annual fees based on pharmaceutical companies’ share of sales to federal healthcare programs, and created a new Patient Centered Outcomes Research Institute to oversee, identify priorities in and conduct comparative clinical effectiveness research, along with funding for such research.

5 unchanged sentences

In addition, in March 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, beginning January 1, 2024.

The rebate was previously cappedat 100% of a drug’s average manufacturer price.

The rebate was previously capped at 100% of a drug’s average manufacturer price.

Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted legislation designed, among other things, to bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical products.

On August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023), and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).

The IRA permits the Secretary of the Department of Health and Human Services (HHS) to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations.

HHS has issued and will continue to issue guidance

implementing the IRA, although the Medicare drug price negotiation program is currently subject to legal challenges.

HHS has issued and will continue to issue guidance implementing the IRA.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

For that and other reasons, it is currently unclear how the IRA will be effectuated.

In addition, individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures and, in some cases, mechanisms to encourage importation from other countries and bulk purchasing.

certain product access and marketing cost disclosure, drug price reporting and other transparency measures and, in some cases, mechanisms to encourage importation from other countries and bulk purchasing.

Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states.

Furthermore, there has been increased interest by third party payors and governmental authorities in reference pricing systems and publication of discounts and list prices.

22 unchanged sentences

regulatory requirements, including U.S.

federal, state and local regulations regarding environmental protection and hazardous and controlled substance controls, among others.

federal, state and local regulations regarding environmental protection and

hazardous and controlled substance controls, among others.

Environmental laws and regulations are complex, change frequently and have tended to become more stringent over time.

7 unchanged sentences

We use a combination of fixed and variable compensation including base salary, cash-based performance bonuses and stock-based compensation awards.

We currently lease a total of approximately 27,280 square feet of office and research and development facilities in Burlingame, California.

7,585 square feet was subleased to Angel Pharmaceuticals through January 2023.

Our lease expires in January 2025 and we believe space will be available to accommodate our future requirements.

We currently lease approximately 20,916 square feet of office and research and development facilities in South San Francisco, California.

This facility lease will expire in February 2028.

We previously leased approximately 27,280 square feet of office and research and development facilities in Burlingame, California.

Approximately 7,585 square feet was subleased to Angel Pharmaceuticals through January 2023.

This facility lease expired in January 2025.

Corporate Information

We were incorporated in Delaware on January 27, 2014 and began operations in November 2014.

Our principal executive offices are located at 863 Mitten Road, Suite 102, Burlingame, California 94010, and our telephone number is (650) 900 4520.

Our principal executive offices are located at 901 Gateway Boulevard, South San Francisco, California 94080, and our telephone number is (650) 900 4520.

Our website address is http://www.corvuspharma.com.

2 unchanged sentences

We take advantage of certain of the scaled disclosures available to smaller reporting companies and will be able to take advantage of these scaled disclosures for so long as the market value of our voting and non-voting common stock held by non-affiliates is less than $250 million measured on the last business day of our second fiscal quarter, or our annual revenue is less than $100 million during the most recently completed fiscal year and the market value of our voting and non-voting common stock held by non-affiliates is less than $700 million measured on the last business day of our second fiscal quarter.

Financial Information about Segments

We view our operations and manage our business as one reportable segment.

See Note 2 to our audited consolidated financial statements included in this Annual Report on Form 10-K.

Additional information required by this item is incorporated herein by reference to Part II, Item 6, “Selected Financial Data.”

Available Information

3 unchanged sentences

The SEC maintains a website that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC.

The address of that website is

The address of that website is www.sec.gov.

The information on or accessible through the SEC and our website is not incorporated into, and is not considered part of, this filing.

1 unchanged sentence

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business