On March 14, 2023 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported a business update and reported financial results for the fourth quarter and full year of 2022 (Press release, Cogent Biosciences, MAR 14, 2023, View Source [SID1234628634]).

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"2022 was a pivotal year for Cogent marked by our promising clinical data with bezuclastinib in systemic mastocytosis, the initiation of our Phase 3 PEAK trial in GIST, and the build-out of the Cogent Research Team," said Andrew Robbins, the company’s President and Chief Executive Officer. "We have laid the foundation for multiple catalysts in 2023 across all our programs. Based on the clinical performance of bezuclastinib, we believe it has the potential to be a best-in-class therapy for patients living with systemic mastocytosis and GIST. We continue to advance therapies that improve the lives of patients with genetically defined rare diseases while positioning ourselves as an industry leader in precision medicine."

Recent Highlights

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In March 2023, Cogent received approvals from European regulatory authorities to initiate the Phase 2 SUMMIT trial in patients with nonadvanced systemic mastocytosis (NonAdvSM). Beginning in April 2023, the company expects to start activating clinical trial sites across major countries in the European Union.
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In December 2022, Cogent reported positive updated clinical data from the ongoing Phase 2 APEX trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.
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As of the cutoff date, October 26, 2022, 11 patients were evaluable for response per the modified IWG-MRT-ECNM criteria. 89% ORR (including centrally adjudicated confirmed and unconfirmed responses) was seen in TKI therapy naïve patients, including 67% of patients achieving CR, CRh or PR, and 22% of patients achieving CR or CRh. Additionally, bezuclastinib demonstrated rapid reductions in serum tryptase, with an 85% mean reduction

in serum tryptase, 14/16 patients achieving ≥ 50% reduction in serum tryptase levels, and eight of these patients achieving serum tryptase of <20ng/mL. Bezuclastinib was generally well-tolerated at all doses. There were no related cases of cognitive impairment and no reported bleeding events, which have been associated with other KIT inhibitors.
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In November 2022, Cogent reported positive clinical lead-in data from the ongoing Phase 3 PEAK trial evaluating bezuclastinib in combination with sunitinib in patients with Gastrointestinal Stromal Tumors (GIST) at the Connective Tissue Oncology Society (CTOS) annual meeting.
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As of the cutoff date, September 26, 2022, 17 of 19 patients remained on study. Early data suggested an encouraging safety and tolerability profile consistent with the previous Phase 1/2 study and the known safety profile for sunitinib monotherapy.
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In October 2022, Cogent reported preclinical data at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) annual meeting on a next-generation fibroblast growth factor receptor 2 (FGFR2) program, which retains potency across all primary, gatekeeper and molecular brake resistance mutations, including N549K and V564I, while sparing FGFR1 inhibition. Also, Cogent presented preclinical data at ENA on a novel ErbB2 mutant selective program which demonstrates robust cellular inhibition of all key resistance and primary driver mutations, including L755S, V842I and S310F/Y, while sparing wild type EGFR target engagement.
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Appointed Rachael Easton, MD, Ph.D., Vice President, Head of Clinical Development. Prior to joining Cogent, Dr. Easton was Group Senior Medical Director, Oncology Clinical Development at GSK​. Prior to GSK, she held clinical development roles of increasing responsibility at Immunocore and Sanofi. Before transitioning into the biotechnology industry, Dr. Easton was an instructor at the University of Pennsylvania School of Medicine where she conducted research in growth and metabolism and provided outpatient care for patients with endocrine disorders.
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Appointed Sylvia Adams, MD to Cogent’s Scientific Advisory Board. Dr. Adams is a Professor of Medicine at the NYU Grossman School of Medicine and Director of the Breast Cancer Center at the Laura and Isaac Perlmutter Cancer Center. As an internationally recognized expert in breast cancer immunotherapy, she has led groundbreaking research and clinical studies leading to the first chemo-immunotherapy approval for breast cancer. She is a member of the ECOG-ACRIN Breast Cancer Committee and at present, co-chairs the NCI Breast Cancer Immuno-Oncology Task Force

Upcoming Milestones

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Present updated clinical data from refractory GIST patients in the lead-in cohort of the Phase 3 PEAK trial of bezuclastinib plus sunitinib during the first half of 2023.
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Provide a mid-year update on the planned initiation of APEX Part 2 based on clinical data from approximately 25-30 patients in APEX Part 1.
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Present initial clinical data from SUMMIT, a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 clinical trial of bezuclastinib in patients with NonAdvSM in the second half of 2023. Clinical data is expected to include safety/tolerability, pharmacokinetics and measures of clinical activity.
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Present updated preclinical data from Cogent’s selective FGFR2 and ErbB2 research programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting taking place April 14-19, 2023 in Orlando, Florida.
Fourth Quarter and Full Year 2022 Financial Results

Cash and Cash Equivalents: As of December 31, 2022, Cogent had cash, cash equivalents and marketable securities of $259.3 million. The company believes that its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2025. Cogent holds a de minimis amount of cash related balances at Silicon Valley Bank.

R&D Expenses: Research and development expenses were $36.7 million for the fourth quarter of 2022 and $121.6 million for the year ended December 31, 2022, as compared to $20.5 million for the fourth quarter of 2021 and $55.9 million for the year ended December 31, 2021. The increase is primarily a result of bezuclastinib clinical trial activities. R&D expenses include non-cash stock compensation expense of $2.4 million for the fourth quarter of 2022 and $8.5 million for the year ended December 31, 2022, as compared to $1.7 million for the fourth quarter of 2021 and $4.4 million for the year ended December 31, 2021.

G&A Expenses: General and administrative expenses were $7.0 million for the fourth quarter of 2022 and $26.2 million for the year ended December 31, 2022, as compared to $5.1 million for the fourth quarter of 2021 and $19.6 million for the year ended December 31, 2021. G&A expenses include non-cash stock compensation expense of $2.6 million for the fourth quarter of 2022 and $9.9 million for the year ended December 31, 2022, as compared to $2.1 million for the fourth quarter of 2021 and $7.3 million for the year ended December 31, 2021

Net Loss: Net loss was $39.6 million for the fourth quarter of 2022 and $140.2 million for the year ended December 31, 2022, as compared to a net loss of $24.9 million for the fourth quarter of 2021 and $72.3 million for the year ended December 31, 2021.

On March 14, 2023 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that it hosted a Key Opinion Leader (KOL) Interview on the interim efficacy results from the OPTIMIZE-1 Phase 2 trial of the company’s lead asset mitazalimab in 1st line metastatic pancreatic cancer, which will be available to view online from Tuesday 14 March, 2023 via this link (Press release, Alligator Bioscience, MAR 14, 2023, View Source [SID1234628633]).

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The discussion features Professor Jean-Luc Van Laethem, Head of the Digestive Oncology Clinic in the Gastroenterology Department of Erasmus Hospital (ULB) Brussels, an internationally-recognized specialist in the field of digestive cancers and the Principal Investigator of the OPTIMIZE-1 trial, and Dr. Sumeet Ambarkhane, Chief Medical Officer of Alligator Bioscience. They discuss perspectives on the current standard of care for patients with metastatic pancreatic cancer, what outcomes are associated with those therapies and the unmet medical needs. The function of mitazalimab and the OPTIMIZE-1 study design are elucidated, and the latest interim efficacy and safety data are presented and explained. Mitazalimab’s therapeutic potential, and other potential combinations with the drug candidate, are discussed as well.

OPTIMIZE-1 is an open-label, multi-center study assessing the safety and efficacy of mitazalimab (CD40 mAb) in combination with chemotherapy, mFOLFIRINOX, in previously untreated patients with metastatic pancreatic ductal adenocarcinoma. In January 2023, Alligator announced strong interim results from OPTIMIZE-1, in which mitazalimab combined with mFOLFIRINOX demonstrated an objective response rate (ORR) of 52% in 23 evaluable patients, as per the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Primary endpoint readout is expected in Q1 2024.

"The potential of mitazalimab as a combination therapy for pancreatic cancer can be seen by comparing these interim results to data from a similar patient population treated only with FOLFIRINIOX, which demonstrated an ORR of around 32 percent," said Dr. Sumeet Ambarkhane, CMO of Alligator Bioscience. "Pancreatic cancer is considered an immunologically cold tumor, meaning there is little influx of T cells which renders therapeutic approaches such as chemotherapy alone less effective. Mitazalimab has an important role to play here because it can activate better infiltration of T cells converting the tumor microenvironment from immune suppressive to immune active, to support the killing of tumor cells."

On March 14, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported the initiation of AIPAC-003 (Active Immunotherapy, Eftilagimod Alpha, and PAClitaxel), an integrated Phase II/III trial to evaluate eftilagimod alpha ("efti") in combination with paclitaxel for the treatment of metastatic HER2-neg/low breast cancer (MBC) (Press release, Immutep, MAR 14, 2023, View Source [SID1234628600]). Regulatory approval has been received in the US and Institutional Review Board (IRB) approval has been received in Spain, with approvals in additional countries anticipated to follow shortly. The first patient is expected to be enrolled in early Q2 CY2023.

As a first-in-class soluble LAG-3 protein targeting MHC Class II ligands on antigen-presenting cells (APC), efti is uniquely positioned to improve clinical outcomes from standard-of-care chemotherapy. Its activation of APCs (e.g., dendritic cells, monocytes) triggers a broad immune response that includes significant increases in cytotoxic CD8+ T cells armed with chemo-induced tumour antigens to target cancer. This synergy was demonstrated by the AIPAC Phase IIb trial’s encouraging efficacy and safety, including a +2.9-month median overall survival (mOS) improvement, statistically significant mOS improvements between 4.2 to 19.6 months across three pre-specified subgroups, a statistically significant increase in cytotoxic CD8 T cells that correlated with improved OS, a higher 48% ORR (vs 38% for chemo alone), and a superior Quality of Life preservation.

Immutep CEO, Marc Voigt, said: "With its novel mechanism of action to activate antigen-presenting cells, efti has to date safely improved clinical outcomes from anti-PD-(L)1 therapies and standard-of-care chemotherapy. We look forward to AIPAC-003 building upon the encouraging synergy seen in our previous Phase IIb trial in metastatic breast cancer, especially with its three key adaptations: same day administration of efti plus paclitaxel, this dual IO-chemotherapy treatment continuing until disease progression, and a new primary endpoint of overall survival. The selected Phase II/III trial design allows us to move forward with a risk-balanced approach in MBC, as we continue our prioritized late-stage clinical development with anti-PD1 therapy in 1st line head & neck squamous cell carcinoma and 1st line non-small cell lung cancer."

The Company and the US Food and Drug Administration (FDA) agreed to the integrated Phase II/III trial design for AIPAC-003 that will help inform a Biologics License Application (BLA). Additionally, the trial design incorporates feedback from Scientific Advice meetings with the European Medicines Agency (EMA) to support a Marketing Authorisation Application (MAA).

Based on feedback from the FDA/EMA, the HR+/HER2-neg/low MBC patient population has been expanded to include triple-negative breast cancer (TNBC), an aggressive cancer with limited treatment options, which together account for ~78% of breast cancer cases. The Company and the FDA also agreed to an open-label lead-in component of 6 to 12 patients to test 90mg efti dosing in combination with paclitaxel driven by efti’s excellent safety profile, along with the FDA’s Project Optimus initiative in oncology. Additionally, patients will receive same-day administration of efti + paclitaxel that can continue until disease progression, unlike the prior AIPAC trial that administered both on different days and stopped chemotherapy at six months.

The open-label lead-in of up to 12 patients will be followed by a randomized (1:1) portion of the Phase II consisting of up to 58 patients that will receive 30mg efti or 90mg efti to determine the optimal biological dose in combination with paclitaxel. Depending on the Phase II results, potential regulatory actions and resources, a randomized, double-blinded, placebo-controlled Phase III portion will then follow. The Phase III will have overall survival as the primary objective and may include a specific patient population.

With respect to the late-stage clinical development of efti, the Phase II portion of the MBC trial, the ongoing randomized/controlled Phase II trial in 1st line HNSCC, and the initiation of the registrational trial in 1st line NSCLC are included in the budget and have no impact on the Company’s expected cash runway to the end of the 1st half of calendar year 2024.

About Eftilagimod Alpha (Efti)
Efti is Immutep’s proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen-presenting cell (APC) activator that stimulates both innate and adaptive immunity for the treatment of cancer. Efti binds to and activates antigen presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and HER2–/HR+ metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

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On March 13, 2023 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, Helmholtz Munich and the Departments of Neurosurgery and Nuclear Medicine at the University Hospital Münster reported the start of a Phase I clinical trial with ITM’s drug candidate ITM-31 (formerly LuCaFab), a novel Targeted Radionuclide Therapy candidate for the treatment of malignant glioblastoma. ITM-31 is a carbonic anhydrase (CA) XII-specific antibody Fab fragment developed by Helmholtz Munich coupled with ITM’s medical radioisotope, non-carrier-added lutetium-177 (n.c.a 177Lu, EndolucinBeta). The investigator-initiated trial (IIT) is sponsored by the University Hospital Münster, conducted in hospitals in Münster, Essen, Cologne, Würzburg, and supported by ITM and Helmholtz Munich. Patient recruitment for the study is ongoing.

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Glioblastoma is a malignant brain tumor with a median survival of approximately 14 to 15 months from diagnosis.1 After treatment with standard therapies (surgery, radio- and chemotherapy), there is a risk that individual tumor cells will remain in the tissue and begin to grow again (relapse). Therefore, treatment of tissue surrounding the tumor is of great importance. ITM-31 has been designed specifically to target residual tumor cells in this surrounding tissue, with the aim of mitigating tumor recurrence.

"A treatment capable of selectively eliminating dormant residual tumor cells after surgical removal of glioblastoma and standard radiochemotherapy gives hope for greater success than with the current standard therapy alone. Intracavitary Radionuclide Therapy with ITM-31 could provide such a treatment opportunity," says Prof. Walter Stummer, Principal Investigator and Chairman of the Department of Neurosurgery at the University Hospital Münster. Study Coordinator Prof. Hans-Jürgen Reulen adds: "Initial compassionate use with ITM-31 (LuCaFab) and previous studies with other radiotherapeutic drug candidates have shown promising results and support the potential of the radiotherapeutic approach for this hard-to-treat cancer type."

The Targeted Radionuclide Therapy candidate ITM-31 targets a specific protein (antigen) called CA XII, which is highly expressed on the cell surface of glioblastoma cells, but not found on healthy brain cells. It comprises a CA XII antibody Fab fragment coupled with the radioisotope 177Lu. ITM-31 is administered directly into the tumor cavity from where it migrates into the surrounding tissue with high specificity, binding to glioblastoma cells which are then irradiated and potentially destroyed while healthy tissue is spared. ITM-31 could thus act as a complementary, adjuvant therapy to the current standard of care approach as it is designed to be applied after initial treatment to glioblastoma to prevent future tumor growth.

"Several published preclinical studies, including ones by our research group, report significant success in the field of Targeted Radionuclide Therapy for brain tumors," comments Prof. Reinhard Zeidler, Project Leader at Helmholtz Munich. "ITM-31, unlike other radionuclide therapies, applies a ‘downsized antibody’, a so-called Fab fragment, which spreads throughout the tissue more easily. Such improved pharmaceutical properties have the potential to create further benefits for the treatment of seriously ill patients living with cancer."

"Together with our partners, our goal is to develop an effective and safe therapeutic option for patients living with this malignant brain tumor," says Steffen Schuster, CEO of ITM. "ITM-31 is a novel treatment approach that is targeted to the cancer cells that evade current treatment regimens, causing glioblastoma to be one of the most aggressive and difficult to treat cancers. This trial is an important first clinical step to developing ITM-31 into a drug potentially capable of circumventing previous hurdles in this high-need indication."

About the Phase I clinical trial with ITM-31
The aim of the dose-escalation study (NCT05533242) with up to 15 patients is to collect data on the efficacy, tolerability, and safety of the investigational drug and to evaluate the best possible patient dose for future studies. Before being treated with ITM-31 in the trial, patients undergo 6 months of standard radio-chemotherapy treatment after surgery. Three single doses of the investigational drug are administered over three months.

(Press release, ITM Isotopen Technologien Munchen, MAR 13, 2023, View Source,_Helmholtz_Munich_and_University_Hospital_M%C3%BCnster_Announce_Start_of_Phase_I_Clinical_Trial_with_Radiotherapeutic_ITM-31_for_Glioblastoma-605/ [SID1234661154])

On March 13, 2023 Patrys reported that a new preclinical study exploiting the novel ability of deoxymabs to enter the cell nucleus to disrupt the cell’s DNA Damage Response (DDR) systems, has validated the potential use of Patrys’ full-sized IgG antibody, PAT-DX3, for synthetic lethality strategies to treat relevant cancers (Press release, Patrys, MAR 13, 2023, View Source [SID1234628683]).

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‘Synthetic lethality’ is a treatment strategy which involves targeting a specific genetic mutation or pathway that is essential for tumour cell survival. In tumours with pre-existing mutations that compromise DDR systems – such as BRCA2 negative breast cancer – adding a deoxymab could make it susceptible to the accumulation of DNA damage, causing tumour cell death.

Patrys’ CEO and Managing Director, Dr James Campbell said:

"This study, requested by a potential partner as part of Patrys’ ongoing business development activities, confirms the potential to use deoxymabs as a single agent to treat cancers which have pre-existing mutations that compromise their DDR systems, including BRCA2 negative breast cancer and other cancers. In addition, Patrys is looking at using deoxymabs in combination with DNA damaging therapies, such as radiation and chemotherapies, and as a delivery agent for small molecules and nucleic acids."