On January 9, 2024 Centessa Pharmaceuticals presented its corporate presentation (Presentation, Centessa Pharmaceuticals, JAN 9, 2024, View Source [SID1234639151]).

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On January 9, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported 2024 priorities to execute against its strategic plan to leverage the benefits of targeted protein degradation across drug discovery and clinical development to create and deliver breakthrough therapies for patients (Press release, C4 Therapeutics, JAN 9, 2024, View Source [SID1234639148]). These priorities capitalize upon recent clinical data and key decisions, resulting in a sharpened focus on executing high-potential programs to ensure achievement of near-term milestones that position C4T for future success.

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Key 2024 priorities include advancing the CFT7455 and CFT1946 clinical programs to value-inflection milestones, supporting CFT8919 Phase 1 development in China by partner Betta Pharmaceuticals, delivering on three discovery collaborations and progressing a streamlined internal discovery effort. As a result of this prioritized portfolio, C4T is restructuring its operations and reducing its workforce by approximately 30%.

C4T has strengthened its balance sheet to ensure sufficient runway to execute through and beyond critical value-inflecting clinical and discovery milestones. C4T has recently received additional capital of approximately $107 million comprised of the previously announced $25 million equity investment from a subsidiary of Betta Pharmaceuticals, the $10 million upfront payment from collaborator Merck for the Degrader-Antibody Conjugate (DAC) collaboration and approximately $72 million in net proceeds generated by leveraging the company’s at-the-market (or ATM) facility. During the fourth quarter of 2023, C4T sold approximately 13.7 million shares under the ATM, at an average price of $5.42 per share, resulting in $72 million of new equity capital, net of commissions and fees.

"Building on recent momentum, we are well positioned to make meaningful advances across our portfolio in 2024. Data from the CFT7455 Phase 1 trial highlighted that the schedule adjustment is yielding expected results, including IMWG responses, and we remain focused on advancing the program to unlock its potential. In addition, we are encouraged by the early pharmacokinetic and pharmacodynamic data from the CFT1946 Phase 1 dose escalation, which confirms oral bioavailability and dose proportional exposure increases, which are associated with deep BRAF degradation," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "Our sharpened focus on progressing CFT7455 and CFT1946 to critical clinical milestones, along with advancing targeted protein degradation research through our discovery collaborations with Roche, Biogen and Merck and our internal research efforts, will help C4T deliver breakthrough therapies for patients with cancer and other diseases. Our strengthened balance sheet, coupled with cost savings from our restructuring, provide sufficient runway to execute through and beyond critical milestones across the portfolio."

Mr. Hirsch continued, "While we believe we are making mission-driven decisions to prioritize our portfolio, restructuring our company and impacting talented colleagues was not a decision we made lightly. We are grateful for their contributions to C4T and are treating our departing colleagues with compassion and support."

2024 ANTICIPATED MILESTONES
The company announced the following key milestones for 2024:

CFT7455

Present updated data from the ongoing Phase 1 dose escalation trial in relapsed/refractory multiple myeloma (R/R MM) in 2H 2024
Present data from the ongoing Phase 1 dose escalation trial in relapsed/refractory non-Hodgkin’s lymphomas (R/R NHL) in 2H 2024
Complete Phase 1 dose exploration in R/R MM and NHL by year-end 2024
CFT1946

Present preclinical data demonstrating differentiated activity in preclinical models of BRAF V600X melanoma, colorectal cancer, non-small cell lung cancer and brain metastasis in 1H 2024
Present data from the ongoing Phase 1 dose escalation trial in melanoma, colorectal cancer, non-small cell lung cancer and other cancers with BRAF V600X mutations in 2H 2024
CFT8919

Support study start-up activities related to the Phase 1 dose escalation trial in EGFR L858R mutated non-small cell lung cancer by partner Betta Pharmaceuticals
RECENT ACHIEVEMENTS

CFT7455

In December 2023, presented positive clinical data from the ongoing CFT7455 Phase 1/2 trial in R/R MM. The data demonstrated anti-myeloma activity, including International Myeloma Working Group (IMWG) responses in patients who have undergone numerous lines of prior therapy for multiple myeloma, including BCMA therapies.
CFT1946

Pharmacokinetic (PK) and pharmacodynamic (PD) data from the initial escalation cohorts of the ongoing CFT1946 Phase 1/2 trial in BRAF V600X mutant solid tumors demonstrate dose proportional exposure and oral bioavailability, which are associated with deep BRAF degradation.
Partnerships
Betta Pharmaceuticals

In January 2024, the previously announced $25 million stock purchase by a subsidiary of partner Betta Pharmaceuticals was completed.
In December 2023, partner Betta Pharmaceuticals received approval from the Chinese National Medical Products Administration for the Investigational New Drug application for CFT8919.
Merck

In December 2023, C4T and Merck entered into a license and research collaboration to discover and develop DACs. Under the terms of the agreement, C4T and Merck will collaborate to develop DACs directed to an initial undisclosed oncology target exclusive to the collaboration; in January 2024, C4T received the $10 million upfront payment for this initial target. C4T is eligible to receive milestone payments totaling approximately $600 million, as well as tiered royalties on future sales, for DACs directed to this initial target.
FINANCIAL GUIDANCE
Unaudited cash, cash equivalents and marketable securities as of January 5, 2024 were approximately $330 million. The company expects that its cash, cash equivalents and marketable securities as of January 5, 2024, together with anticipated cost savings from the restructuring, will enable the company to fund its operating plan into 2027.

J.P. MORGAN PRESENTATION
C4T will present at the 42nd Annual J.P. Morgan Healthcare Conference on Thursday, January 11, 2024 at 9:00 am PST (12:00 pm EST). A live webcast will be available under "Events & Presentations" in the Investors section of the company’s website at www.c4therapeutics.com. A replay of the webcast will be archived on the C4T website for at least two weeks following the presentation.

On January 9, 2024 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported its full year 2024 revenue guidance as part of its outlined 2024 strategic priorities today at the 42nd Annual J.P. Morgan Healthcare Conference in San Francisco, California (Press release, BioNTech, JAN 9, 2024, View Source [SID1234639147]).

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"At BioNTech, we are making important strides towards building a global immunotherapy company. In 2023, we continued our vaccine leadership in the fight against COVID-19 and significantly expanded our mid- and late-stage oncology pipeline. Currently, late-stage trials are ongoing in multiple oncology indications, and we plan to have ten or more potentially registrational trials in our pipeline by the end of 2024," said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "This year will be a year of significant execution at BioNTech as we continue to expand and develop our innovative pipeline towards our first oncology launches expected from 2026 onwards."

Prof. Ugur Sahin, M.D., will present a corporate overview and update at the 42nd Annual J.P. Morgan Healthcare Conference on Tuesday, January 9, 2024, at 6:00 p.m. CET/ 12:00 p.m. ET. A live webcast of the presentation will be available on the "Events & Presentations" page in the Investor Relations section on the Company’s website. The replay of the webcast will be archived on the Company’s website for 30 days following the conference.

2024-2026 Financial Framework

BioNTech projects total company revenues of approximately €3 billion for the financial year 2024, mainly driven by the COVID-19 vaccine franchise which is expected to remain profitable given the Company’s cost sharing structure with its partner Pfizer Inc. ("Pfizer"). The Company plans to provide detailed full year 2024 financial guidance during its Full Year and Fourth Quarter 2023 Financial Results call on Wednesday, March 20, 2024.

BioNTech ended 2023 with approximately €17.5 billion (unaudited) in cash, cash equivalents and security investments. The Company plans to maintain a strong financial position and generate significant interest income in 2024. BioNTech expects to grow its topline again in 2025. In the outer years, the Company projects revenues derived from both oncology and respiratory combination vaccine launches, which are subject to successful development and regulatory approval.

As a science and innovation driven company, BioNTech will continue to focus investments on R&D and scaling the business for commercial readiness in oncology in multiple countries by the end of 2025 while continuing to be cost disciplined.

Summary of Selected Pipeline Updates and Expected Milestones

COVID-19 & Other Infectious Diseases

BioNTech’s infectious disease portfolio seeks to address four key areas of high medical need: respiratory viruses, latent viruses, global health pathogens, and antimicrobials. The Company has established a broad early-stage infectious disease vaccine candidate pipeline containing seven clinical programs leveraging its mRNA technology.

BNT162b2 + BNT161 is an mRNA-based combination vaccine program against COVID-19 and influenza being developed in collaboration with Pfizer. Topline data from the Phase 1/2 trial (NCT05596734) demonstrated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains and that the safety profile of the candidates was consistent with the companies’ COVID-19 vaccine.

Oncology

In 2023, BioNTech made significant progress in demonstrating the potential of its oncology programs as part of its in-house discovery and development efforts and added six new clinical assets, including next generation antibody-drug conjugate (ADC) candidates and antibody programs, to the Company’s oncology pipeline through internal and collaborative efforts. The Company’s pipeline continued to mature in 2023 with various programs advancing towards later stages of development. BioNTech’s pipeline currently contains 11 ongoing Phase 2 and 3 trials.

Selected later-stage programs:

BNT323/DB-1303 is an HER2-targeted antibody-drug conjugate candidate being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. ("DualityBio"). First-in-human data from an ongoing Phase 1/2 trial (NCT05150691) demonstrated anti-tumor activity in patients with heavily pretreated HER2-expressing solid tumors. In December 2023, the U.S. Food and Drug Administration ("FDA") granted Breakthrough Designation for BNT323/DB-1303 for the treatment of advanced endometrial cancer in patients who progressed on or after treatment with immune checkpoint inhibitors. A pivotal Phase 3 trial (NCT06018337) in patients with Hormone Receptor-positive ("HR+") and HER2-low metastatic breast cancer that have progressed on hormone and/or cyclin-dependent kinase 4/6 ("CDK4/6") therapy is planned. Additional potentially registrational trials are planned to be initiated in 2024.

BNT316/ONC-392 (gotistobart) is a next-generation anti-CTLA-4 monoclonal antibody candidate jointly developed by BioNTech and OncoC4, Inc. ("OncoC4"). A pivotal Phase 3 trial (NCT05671510) evaluating BNT316/ONC-392 (gotistobart) in patients with immunotherapy-experienced non-small cell lung cancer (NSCLC) is ongoing.

BNT327/PM8002 (PD-L1xVEGF) is an anti-VEGF-A antibody candidate fused to a humanized anti-PD-L1 VHH being developed in collaboration with Biotheus Inc. ("Biotheus"). BNT327/PM8002 is currently being evaluated in several Phase 2/3 studies in China to assess the efficacy and safety of the candidate as a monotherapy or in combination with chemotherapy in various indications. Trial data are planned to be presented this year at a medical conference, and an Investigational New Drug application has been accepted by the FDA for further studies in the U.S. A potentially registrational trial is planned in 2024.

BNT311/GEN1046 (acasunlimab) is a potential first-in-class bispecific antibody candidate combining PD-L1 checkpoint inhibition with 4-1BB costimulatory activation being developed in collaboration with Genmab S/A ("Genmab"). Based on emerging clinical data, the companies have planned engagement with health authorities on the design of a Phase 3 trial for BNT311/GEN1046 (acasunlimab) in second line NSCLC. The companies intend to share the data on which this decision was based at a medical conference in 2024.

BNT312/GEN1042 is a potential first-in-class bispecific antibody candidate designed to induce conditional immune activation by crosslinking CD40 and 4-1BB positive cells, also being developed in collaboration with Genmab. Data required to determine next steps for this program are planned to be shared at a medical conference in 2024.

BNT122 (autogene cevumeran) is an mRNA cancer vaccine candidate based on an individualized neoantigen-specific immunotherapy (iNeST) approach being developed in collaboration with Genentech Inc. ("Genentech"), a member of the Roche Group. In October 2023, BioNTech announced the initiation of IMCODE003, a Phase 2 trial (NCT05968326) evaluating the efficacy and safety of autogene cevumeran in combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and standard of care chemotherapy in patients with resected pancreatic ductal adenocarcinoma. This is the third indication for which autogene cevumeran is being evaluated in a Phase 2 trial, alongside other ongoing studies in first-line melanoma and adjuvant colorectal cancer. An additional Phase 2 trial is planned to be initiated as early as late 2024.

BNT211 consists of two investigational medicinal products: a CAR-T cell product candidate targeting Claudin-6 (CLDN6)-positive solid tumors, in combination with a CAR-T cell-amplifying RNA vaccine (CARVac) encoding CLDN6. BioNTech plans to initiate a pivotal Phase 2 trial in relapsed/refractory germ cell tumors in 2024.

In 2024, BioNTech intends to accelerate the development of its portfolio of next-generation investigational medicines both as monotherapies and in combination with immunotherapy agents and other targeted therapies across a wide range of tumor types. BioNTech believes it is well positioned to have ten or more potentially registrational trials in areas of unmet medical need by the end of 2024 in advance of launching its first oncology products from 2026 onwards.

Upcoming Investor and Analyst Events

Full Year and Fourth Quarter 2023 Financial Results: March 20, 2024
Annual General Meeting: May 17, 2024

On January 9, 2024 Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported that Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board, will present recent clinical progress and 2024 corporate milestones at the 42nd Annual J.P. Morgan Healthcare Conference on Tuesday, January 9, 2024 from 8:15 am – 8:55 am PST (Press release, Biomea Fusion, JAN 9, 2024, View Source [SID1234639146]).

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A live webcast of the presentation will be available on the Investors & Media page of Biomea’s website at: View Source

"2023 was a truly remarkable year for Biomea as we had several positive data readouts in both type 2 diabetes and AML. Meanwhile, we initiated the expansion portion of the type 2 diabetes trial and received IND and CTA clearance for type 1 diabetes and have just now dosed our first patient in that study. Our second pipeline asset BMF-500 was also advanced into the clinic and is enrolling steadily," stated Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board. "We believe BMF-219 has the potential to address the root cause of diabetes and modify its progression in patients. Our goal is to develop a short-term treatment that will reconstitute insulin producing beta cells and thereby allow a patient with diabetes to normalize blood sugar levels in a natural way. Over the past months, we have built out our team and the necessary study sites to fully explore the potential utility of BMF-219 across the different subtypes of diabetes patients. In 2024, we are planning to complete the dosing and follow-up of over 200 expansion cohort patients. This data is expected to provide the foundation for registrational studies in type 2 diabetes, which we plan to start in 2025. We are also set up to explore BMF-219’s potential in type 1 diabetes with our Phase 2 study, COVALENT-112, and will share data from the 40 patient open label portion within this year. And finally, we will continue the patient enrollment in our liquid and solid tumor studies and anticipate completing the dose escalation steps in each of the cohorts within this year. 2024 will be an exciting year for Biomea and we are looking forward to providing you continued updates throughout as we further define a registrational path forward for each of our diabetes and oncology assets."

RECENT UPDATES & ANTICIPATED 2024 MILESTONES

DIABETES

COVALENT-111 (BMF-219 for Type 2 Diabetes)

Presented proof-of-concept clinical data in a Phase II study with only 4 weeks of dosing:
Compared to baseline, 84% of all type 2 diabetes patients dosed for four weeks with BMF-219 showed a reduction in HbA1c at Week 4 and 74% at Week 12 (n=32), two months after the final dose of BMF-219. 60% of type 2 diabetes patients dosed with 100 mg achieved a controlled HbA1c of 7% or below at the end of Week 12, two months after the last dose of BMF-219, and 36% of type 2 diabetes patients in the 200 mg cohorts showed a durable HbA1c reduction of 1% or more at Week 26, five months after the last dose of BMF-219.
FDA and Health Canada cleared the initiation of the expansion portion of the Phase II study, which will evaluate BMF-219 administered at 100 mg and 200 mg, with dosing durations up to 12 weeks in a minimum of 216 type 2 diabetes patients.
Anticipated 2024 Milestones:

On track to complete escalation portion of COVALENT-111 and present 26-week data, five months after last dose of BMF-219, from cohorts (50 mg, 100 mg, and 200 mg) that were dosed with BMF-219 for 28 days, at the Advanced Technologies and Treatments for Diabetes Meeting in March 2024.
On track to finish enrolling three expansion cohorts of COVALENT-111 and provide initial data in 2024
COVALENT-112 (BMF-219 for Type 1 Diabetes)

FDA and Health Canada cleared the IND / CTA for Phase II study COVALENT-112 of BMF-219 in type 1 diabetes. The study is designed to enroll 150 adults with type 1 diabetes and examine the safety and efficacy of BMF-219 at two oral dose levels, 100 mg and 200 mg, for 12 weeks of treatment followed by a 40 week off-treatment period. The trial will also include an open label portion (n=40), enrolling participants with type 1 diabetes up to 15 years since diagnosis.
Dosed the first type 1 diabetes patient in COVALENT-112.
Anticipated 2024 Milestones:

Complete enrollment of the open label portion (n=40).
On track to establish the initial proof of concept based on clinical data in type 1 diabetes patients treated in COVALENT-112 with BMF-219.
ONCOLOGY

COVALENT-101 (BMF-219 for Liquid Tumors)

Presented initial Phase I topline data in AML with first complete responder achieving Minimal Residual Disease negativity.
Continued patient enrollment exploring BMF-219’s utility in liquid tumors (AML/ALL, MM, CLL, DLBCL).
Anticipated 2024 Milestones:

On track to complete dose escalation portion of COVALENT-101 in liquid tumors and establish recommended Phase II dose.
COVALENT-102 (BMF-219 for KRAS-Mutant Solid Tumors)

Continued patient enrollment exploring BMF-219’s utility in KRAS driven solid tumors (PDAC, NSCLC, CRC).
Anticipated 2024 Milestones:

On track to complete dose escalation portion of COVALENT-102 in solid tumors and establish recommended Phase II dose.
COVALENT-103 (BMF-500 for Acute Leukemias)

Announced FDA clearance of IND for BMF-500 and started enrollment of leukemia patients with FLT3 mutations.
Anticipated 2024 Milestones:

On track to complete dose escalation portion of COVALENT-103 and establish recommended Phase II dose.
FUSION SYSTEM DISCOVERY PLATFORM

Built out and opened new lab facilities to validate and progress in-house research efforts.
Continued the development of the Biomea FUSION Platform technology.
Anticipated 2024 Milestones:

On track to announce a third development candidate from the Biomea FUSION Platform technology.

On January 8, 2024 Pasithea Therapeutics Corp. (NASDAQ: KTTA) ("Pasithea" or the "Company"), a clinical stage biotechnology company focused on the discovery, research, and development of innovative treatments for Central Nervous System (CNS) disorders, reported the invention of a crystalline form of PAS-004 which is captured in polymorph and stereoisomer patent filings that when issued we believe will extend patent protection to at least 2045 (Press release, Pasithea Therapeutics, JAN 8, 2024, View Source [SID1234640980]).

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Chief Development Officer Dr. Graeme Currie stated, "Through the invention of the crystal structure for PAS-004 and subsequent patent filings, we are pleased to extend and strengthen the PAS-004 patent portfolio which we believe extends current protection from 2032 to at least 2045. We worked closely with Jones Day, a top global law firm with a premier IP biotech practice, to reach this important milestone."

Chief Executive Officer Dr. Tiago Reis Marques added, "Through additional chemistry, manufacturing, and controls (CMC) development we believe that we continue to increase the value of PAS-004. We are pleased that our upcoming phase 1 dose escalation trial will utilize the newly invented crystalline drug substance."

About PAS-004

PAS-004 is a small molecule allosteric inhibitor of MEK 1/2, which are dual-specificity protein kinases, in the MAPK signaling pathway. The MAPK pathway has been implicated in a variety of diseases, as it functions to drive cell proliferation, differentiation, survival and a variety of other cellular functions that, when abnormally activated, are critical for the formation and progression of tumors, fibrosis and other diseases. MEK inhibitors block phosphorylation (activation) of extracellular signal-regulated kinases (ERK). Blocking the phosphorylation of ERK can lead to cell death and inhibition of tumor growth. Existing FDA approved MEK inhibitors are marketed for a range of diseases, including certain cancers and neurofibromatosis type 1 (NF1). We believe these MEK inhibitors suffer from certain limitations, including known toxicities. Unlike current FDA approved MEK inhibitors, PAS-004 is macrocyclic, which we believe may lead to improved pharmacokinetic and safety (tolerability) profiles. Cyclization offers rigidity for stronger binding with drug target receptors. PAS-004 was designed to provide a longer half-life with what we believe is a better therapeutic window. Further, we believe the potency and safety profile that PAS-004 has demonstrated in preclinical studies may also lead to stronger and more durable response rates and efficacy, as well as better dosing schedules. PAS-004 has been tested in a range of mouse models of various diseases and has completed preclinical testing and animal toxicology studies. Additionally, PAS-004 has received orphan-drug designation from the FDA for the treatment of NF1.