On March 19, 2024 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS) (GLOBAL NEWSWIRE), a clinical-stage biopharmaceutical company, reported a business update and reported financial results for the fourth quarter and year ended December 31, 2023 (Press release, Corvus Pharmaceuticals, MAR 19, 2024, View Source [SID1234641259]).

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"Corvus is pioneering the development of ITK inhibition with a focus on advancing our lead program, soquelitinib, into a registrational Phase 3 trial for patients with relapsed PTCL," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We believe we are well positioned to execute on this trial, with recent positive updates from our Phase 1/1b clinical trial, alignment on the final study protocol with FDA, interest from leading academic centers in North America, and the receipt of Orphan Drug Designation for soquelitinib. We also continue to expand our knowledge and experience with ITK-mediated immunomodulation as a novel therapeutic for a broad range of cancers and immune diseases. We have several exciting opportunities in immunology, including plans for a randomized, placebo controlled clinical trial of soquelitinib in atopic dermatitis. In addition, we continue to progress our next-generation ITK inhibitors, which have been designed to optimize T cell modulation for specific immune indications. Based on current timelines, we anticipate the atopic dermatitis trial will be initiated in the second quarter of 2024 with initial data potentially available by year end, and we anticipate the PTCL trial will be initiated in the third quarter."

Business Update and Strategy

Prioritized Program: Soquelitinib (formerly CPI-818, Corvus’ selective ITK inhibitor)

Soquelitinib for T Cell Lymphoma

Corvus continues to follow patients with relapsed T cell lymphoma in a Phase 1/1b clinical trial evaluating single agent therapy with soquelitinib. Updated interim data as of January 22, 2024 (data shown below in Figures 1-2):
A total of 23 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose and meet the eligibility criteria for the planned registrational Phase 3 clinical trial based on ≥1 and ≤3 prior therapies (eligible patient population), including 21 evaluable patients.
For the 21 evaluable patients, objective responses (complete response, CR plus partial response, PR) were seen in seven patients, including four CRs and three PRs. Compared to the prior data (as of November 21, 2023) reported from the trial in December 2023 in conjunction with the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, one of the patients achieving a PR continued to respond and achieved a CR.
Disease control (CR, PR and stable disease) was seen in 12 of 21 patients. The stable disease group included five patients who achieved tumor reductions that did not meet the criteria for a PR, with two of these patients continuing to receive therapy. Several patients experiencing tumor regression are continuing to receive therapy.
The Company presented a poster at ASH (Free ASH Whitepaper) that included additional data from the Phase 1/1b clinical trial and complementary preclinical data, including the evaluation of blood samples and tumor biopsies from eight patients who participated in the trial. The results support soquelitinib’s novel mechanism of action, and demonstrated increases in cytotoxic killer T cells and reductions in markers of T cell exhaustion.
Figure 1: Waterfall Plot for Patients in the 200 mg Dose Cohort of the Soquelitinib 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 (eligible patient population), as of January 22, 2024, that were measurable by CT scan or by Modified Severity-Weighted Assessment Tool (mSWAT) for patients with cutaneous involvement.

Waterfall Plot for Patients in the 200 mg Dose Cohort of the Soquelitinib 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 (eligible patient population), as of January 22, 2024, that were measurable by CT scan or by Modified Severity-Weighted Assessment Tool (mSWAT) for patients with cutaneous involvement.

Figure 2: Swimmer Plot of Eligible Patient Population 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 fungoides type; NKTCL, natural killer cell T cell lymphoma; ALCL, anaplastic large cell lymphoma; AITL, angioimmunoblastic T cell lymphoma.

Swimmer Plot of Eligible Patient Population 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 fungoides type; NKTCL, natural killer cell T cell lymphoma; ALCL, anaplastic large cell lymphoma.

In February 2024, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for soquelitinib for the treatment of T cell lymphoma, providing potential benefits including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and seven years of post-approval marketing exclusivity. The Company has also obtained alignment with FDA on its protocol for a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed PTCL and anticipate initiating the trial in the third quarter of 2024. There are currently no FDA fully approved agents for the treatment of relapsed PTCL.
Soquelitinib for Immune Diseases

Corvus plans to initiate a randomized, placebo-controlled Phase 1 trial of soquelitinib in patients with moderate to severe atopic dermatitis in the second quarter of 2024, with the potential for initial data from the trial before year end 2024. The trial is planned to enroll 64 patients that have failed at least one prior therapy across four different 28-day dosing regimens of soquelitinib compared to a placebo group. The endpoints include safety and improvement in Eczema Area and Severity Index ("EASI"). Patients and physicians will be blinded to treatment assignment.
In February 2024, Corvus presented preclinical data for soquelitinib at the Keystone Symposia on Systemic Autoimmunity and Autoinflammatory Diseases. The data included the first description of Corvus’ next-generation ITK inhibitor preclinical product candidates, which were designed to deliver precise T-cell modulation that is optimized for specific immunology indications. These preclinical product candidates exhibit specific biologic properties that are anticipated to enable more precise inhibition of Th1, Th2 and/or Th17 cell function. Atopic dermatitis and asthma are thought to be mediated primarily by Th2 lymphocytes. Th17 cells are associated with psoriasis and psoriatic arthritis. The results suggest that chemical structures may be refined to perform more specific biologic functions and may enable targeting of various types of immune disease. This data builds on the publication of preclinical data on soquelitinib as a preprint at bioRxiv in November 2023 that demonstrated ITK’s selective inhibition which produced therapeutic benefits in several autoimmune and allergy preclinical models including psoriasis, asthma, pulmonary fibrosis, scleroderma and graft versus host disease.
In February 2024, the Company appointed Jeffrey Arcara as Chief Business Officer, with responsibility for leading corporate strategy, business development, portfolio strategy, and new product planning. This includes an initial focus on maximizing the potential of the Company’s ITK inhibitor programs, both internally and through partnerships. Mr. Arcara previously served as senior vice president, head global marketing & portfolio and strategy for the innovative medicines and biosimilars business at Teva Pharmaceuticals.
Partner Led Programs: Ciforadenant (adenosine 2a receptor inhibitor) and Mupadolimab (anti-CD73)

The Kidney Cancer Research Consortium is enrolling a Phase 1b/2 clinical trial evaluating ciforadenant as a potential first line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The Phase 1b portion of this trial has been completed and patients are now being enrolled in the Phase 2 portion. The clinical trial is expected to enroll up to 60 patients and initial data is anticipated in the first half of 2024.
Angel Pharmaceuticals, Corvus’ partner in China, is enrolling patients in a Phase 1/1b clinical trial of mupadolimab in patients with non-small cell lung cancer (NSCLC) and head and neck squamous cell cancers (HNSCC). In this clinical trial, patients will receive mupadolimab monotherapy or in combination with pembrolizumab.
Financial Results
As of December 31, 2023, Corvus had cash, cash equivalents and marketable securities of $27.1 million as compared to $42.3 million as of December 31, 2022. During the year ending December 31, 2023, the Company sold 2,461,903 shares of its common stock through its at-the-market program, generating net proceeds to the Company of approximately $7.8 million.

Research and development expenses for the three months and full year ended December 31, 2023 totaled $4.0 million and $16.5 million, respectively, compared to $4.1 million and $24.5 million for the same periods in 2022. For the full year 2023, the decrease of $8.0 million was primarily due to lower clinical trial and manufacturing costs associated with the development of mupadolimab.

The net loss for the three months ended December 31, 2023 was $6.7 million compared to a net loss of $9.8 million for the same period in 2022. Total stock compensation expense for the three months ended December 31, 2023 and 2022 was $0.6 million and the non-cash loss from Corvus’ equity method investment in Angel Pharmaceuticals was $1.4 million for the three months ended December 31, 2023 compared to $4.6 million in the same period in 2022.

Conference Call Details
Corvus will host a conference call and webcast today, Tuesday, March 19, 2024, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the fourth quarter and full year 2023 financial results. The conference call can be accessed by dialing 1-877-407-0784 (toll-free domestic) or 1-201-689-8560 (international) or by clicking on this link for instant telephone access to the event. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.

On March 19, 2024 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that results of its preclinical studies on ATG-101 (PD-L1/4-1BB bispecific antibody) were published in Cancer Research in a paper titled ATG-101 is a tetravalent PD-L1×4-1BB bispecific antibody that stimulates anti-tumor immunity through PD-L1 blockade and PD-L1-directed 4-1BB activation[1] (Press release, Antengene, MAR 19, 2024, View Source [SID1234641276]). Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), publishes impactful original studies, reviews, and opinion pieces of high significance to the broad cancer research community. It has a 5-year impact factor of 13.

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"Although immune checkpoint inhibitors (ICIs) have transformed cancer treatment, many patients do not achieve desired treatment outcomes due to innate or acquired resistance," said Dr. Bing Hou, Antengene’s Head of Discovery Science & Translational Medicine, and the corresponding author of the paper. "While 4-1BB has been recognized as a powerful immune stimulating target, the development of therapeutic 4-1BB agonists has been hampered by hepatotoxicity and suboptimal efficacy. In the Cancer Research paper, we present studies used to characterize the differentiated preclinical features and mechanism of action of ATG-101, a tetravalent PD-L1/4-1BB bispecific antibody. ATG-101 activates 4-1BB+ T cells in a PD-L1-crosslinking dependent manner, which minimizes the hepatotoxicity associated with existing 4-1BB agonists and suppresses the growth of ICI-resistant tumors. We wish to continue contributing to the academic community through publications in the future."

"The dedication and relentless efforts of our research team have led to the publication of the preclinical work in the prestigious journal Cancer Research and the development of a new clinical program," said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO." The Phase I study of ATG-101 is currently in the sixth dose escalation cohort and the drug is approaching its biologically active dose with good tolerability. Early observations indicate that a partial response has been observed in a patient with microsatellite stable (MSS) metastatic colon adenocarcinoma with liver metastasis. Moreover, there have also been multiple patients with durable stable disease. These early observations are indeed very encouraging. Moving forward, we will continue working closely with the study sites and investigators to bring a new treatment option to patients who have previously relapsed/progressed on ICIs."

Reference

[1] ATG-101 is a tetravalent PD-L1×4-1BB bispecific antibody that stimulates anti-tumor immunity through PD-L1 blockade and PD-L1-directed 4-1BB activation. Cancer Res (2024). DOI:10.1158/0008-5472.CAN-23-2701.

About ATG-101

ATG-101 is a novel PD-L1/4-1BB bispecific antibody that was designed to block the binding of immunosuppressive PD-1/PD-L1 and conditionally induce 4-1BB stimulation, thus activating anti-tumor immune effectors, while delivering enhanced anti-tumor activity, with an improved safety profile. ATG-101 is currently being developed in Australia, China, and the U.S. in the Phase I study for the treatment of advanced/metastatic solid tumors and B-cell non-Hodgkin lymphoma (B-NHL).

On March 19, 2024, Intellia Therapeutics, Inc. (the "Company" or "Intellia") notified Regeneron Pharmaceuticals, Inc. ("Regeneron") reported that the Company is opting out of its Factor IX Co-Development and Co-Funding Agreement (the "Co-Co Agreement"), which the Company and Regeneron entered into in May 2020 (Filing, 8-K, Intellia, MAR 19, 2024, View Source [SID1234641383]). The Co-Co Agreement will terminate 180 days after Intellia provided written notice to Regeneron, and the Company will continue to have obligations under the Co-Co Agreement related to the co-development of gene editing products directed to factor IX until the effective date of termination. Upon termination, the Company will no longer be obligated for sharing 35% of the development costs, or be entitled to receive 35% of the profits, for gene editing products directed to factor IX under the Co-Co Agreement. In addition, after termination of the Co-Co Agreement Intellia would continue to support Regeneron with the development of gene editing products directed to factor IX, as applicable, under the License and Collaboration Agreement between the Company and Regeneron, dated April 11, 2016, as amended (the "LCA"), and the LCA will control the parties’ obligations to develop and commercialize gene editing products directed to factor IX, including any milestone payments and royalties that would be owed to the Company if Regeneron develops and commercializes such products and the intellectual property licenses and other rights related to such products. Under the LCA, Intellia may be eligible to receive up to $320.0 million in milestone payments and royalties in the high-single digits to low teens, which royalties are potentially subject to various reductions, offsets and upstream payment obligations. The termination of the Co-Co Agreement does not affect any other target or programs that are the subject of the Company’s collaboration with Regeneron under the LCA or any other co-development and co-funding agreement with Regeneron.

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The foregoing summary is qualified in its entirety by reference to the form of Co-Development and Co-Promotion Agreement which the Company filed as Exhibit 10.16 to its Annual Report on Form 10-K for the year ending December 31, 2023.

On March 19, 2024 Curium, a world leader in nuclear medicine, reported that in the Netherlands the first commercial dose of PYLCLARI has been sold (Press release, Curium, MAR 19, 2024, View Source [SID1234641260]). PYLCLARI (INN: Piflufolastat (18F) also known as (18 F)-DCFPyL, is indicated for the detection of prostate-specific membrane antigen (PSMA) positive lesions with positron emission tomography (PET) in patients with prostate cancer in the following clinical settings:

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Primary staging of patients with high-risk prostate cancer prior to initial curative therapy
To localize recurrence of prostate cancer in patients with a suspected recurrence based on increasing serum prostate-specific antigen (PSA) levels after primary treatment with curative intent
Benoit Woessmer, PET Europe CEO at Curium commented, "We are pleased that with today’s news of first commercial supply in the Netherlands, PYLCLARI is now available to more nuclear medicine physicians and their patients in three European countries – Greece, Italy, and in the Netherlands where the production will be done by our partner BV Cyclotron VU in Amsterdam. With our focus on redefining the experience of cancer through our trusted legacy in nuclear medicine, Curium is proud to be improving the choice of diagnostic modalities available to our customers across Europe – ultimately for the benefit of patients with prostate cancer."

Today’s announcement follows the decision in July 2023 by the European Commission granting marketing authorization for PYLCLARI in the European Union, followed by first commercial doses in Greece in November 2023, and in Italy in February 2024.

On March 19, 2024 Mabwell (688062.SH), an innovative-driven biopharmaceutical company with entire industry chain, reported the clinical study data of the 9MW2821 for patients with cervical cancer as focused plenary oral presentation at the Society of Gynecologic Oncology (SGO) annual meeting on March 16, 2024 (Press release, Mabwell Biotech, MAR 19, 2024, View Source;the-first-published-clinical-data-of-nectin-4-targeting-adc-developed-by-mabwell-in-cervical-cancer-demonstrates-its-outstanding-therapeutic-potential-302092792.html [SID1234641277]).

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The data showed good efficacy and safety of 9MW2821 in patients with cervical cancer, which is expected to bring new breakthroughs for the treatment of recurrent or metastatic cervical cancer, meeting a large number of unmet clinical needs.

9MW2821 is the first drug to report clinical data for the indication of cervical cancer among the drugs with the same target in the world.

Report on Study Data of Nectin-4-Targeting Antibody-drug Conjugate (ADC) for the Treatment of Recurrent or Metastatic Cervical Cancer

This phase I/II, multicenter, open-label, clinical study was led by Professor Zhang Jian of Fudan University Shanghai Cancer Center, and Professor Yang Huijuan of Fudan University Shanghai Cancer Center represented the study team to give an in-depth report at the meeting. The study results were highly recognized by experts on site. Further clinical study data are expected to provide more treatment options for patients with recurrent or metastatic cervical cancer.

Clinical Findings

The systemic treatment drug options and efficacy for recurrent or metastatic cervical cancer are relatively limited. The cervical cancer cohort in the phase I/II study of 9MW2821 enrolled patients with Nectin-4-positive recurrent or metastatic cervical cancer who had progressed on or after doublet platinum-containing chemotherapy with or without bevacizumab and received no more than two previous systemic regimens for recurrent or metastatic disease. Eligible patients received intravenous 9MW2821 1.25mg/kg on days 1, 8 and 15 of each 28-day cycle until confirmed disease progression, death, intolerable adverse effects or withdrawal from the study.

As of September 25, 2023, in the cervical cancer expansion cohort of the study, the detection rate of Nectin-4 expression was 89.67%, and the rate of Nectin-4 IHC 3+ was 67.82%. A total of 40 patients were enrolled in the study, 57.5% of the patients had previously received platinum-based doublet chemotherapy combined with bevacizumab, and 60% of the patients had previously received platinum-based doublet chemotherapy and immune checkpoint inhibitor therapy.

In terms of efficacy, the overall response rate (ORR) and disease control rate (DCR) of 37 patients evaluable for efficacy were 40.54% and 89.19%, respectively, with one complete response (2.70%) and 14 partial responses (37.84%). Median progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were not reached yet. Among patients with Nectin-4 IHC 3+, the ORR and DCR of 26 patients evaluable for efficacy were 50.00% and 92.31%, respectively. Among patients on or after doublet platinum-containing chemotherapy, the ORR and DCR of 21 patients evaluable for efficacy were 38.10% and 85.71%, respectively.

In terms of safety, treatment-related adverse events (TRAEs) occurred in 92.50% of participants. Grade3-4 TRAEs occurred in 70.00% of participants, with neutropenia (40.00%), rash (17.50%) and gamma-glutamyl transferase increased (12.50%) being the most frequently reported. Nodeaths related to treatment were reported.

The above study results indicate that 9MW2821 has controllable safety and positive efficacy in patients with cervical cancer.

About 9MW2821

9MW2821 is the first site-specific conjugated novel ADC targeting Nectin-4 developed by Mabwell using ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, and is the first product to enter clinical study among the products with the same target developed by Chinese companies. Multiple clinical studies of 9MW2821 have been conducted in China to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of 9MW2821 in patients with various advanced solid tumors.

The phase III clinical study of 9MW2821 monotherapy has officially been initiated in patients with locally advanced or metastatic urothelial carcinoma who have previously received platinum-based chemotherapy and PD-(L)1 inhibitor therapy. The phase I/II clinical study of 9MW2821 in combination with PD-1 inhibitors is also ongoing, with the first patient already enrolled. The phase II clinical study for the indication of esophageal carcinoma will continue enrollment and evaluation, and communication for the initiation of phase III clinical study will be expedited. 9MW2821 was granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) in February 2024 for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma. Currently, 9MW2821 is the first therapeutic drug targeting Nectin-4 in the world to disclose clinical efficacy and safety data for indications of cervical cancer and esophageal carcinoma.

About Cervical Cancer

Cervical cancer is the 4th most common neoplasm and the 4th leading cause of cancer death in females worldwide (excerpted from "Worldwide trends in cervical cancer incidence and mortality, with predictions for the next 15 years, Cancer 2021"). According to the "World Cancer Report 2020" released by the International Agency for Research on Cancer (IARC), there were 600 thousand new cases of cervical cancer worldwide in 2020 and up to 340 thousand deaths caused by cervical cancer. In February 2024, the National Cancer Center published the Cancer Burden Data in China in 2022 on Journal of the National Cancer Center (JNCC), showing that there were 150.7 thousand new cases of cervical cancer and 55.7 thousand deaths in China, ranking 8th and 9th respectively in terms of new cases and number of deaths. Compared with the 119 thousand new cases and 37 thousand deaths released in February 2022 for the same period in 2016, significant increases are observed.