On January 15, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI343, a potentially best-in-class TOPO1i anti-CLDN18.2 ADC, as monotherapy for the treatment of CLDN18.2-positive advanced pancreatic ductal adenocarcinoma (PDAC) patients who have progressed after at least one line of prior systematic treatment (Press release, Innovent Biologics, JAN 15, 2025, View Source [SID1234649747]).

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The BTD for IBI343 was granted based on data from an ongoing Phase 1 study conducted in China, Australia and the U.S. (NCT05458219), which demonstrated favorable safety and tolerability, as well as promising antitumor activity of IBI343 monotherapy in advanced PDAC patients. Data from the study’s dose-expansion cohort were presented orally at the 2024 ESMO (Free ESMO Whitepaper) Asia Congress:

A total of 43 patients with CLDN18.2-positive advanced PDAC (≥60% tumor cells with membranous staining intensity ≥1+ by IHC) received IBI343 6 mg/kg Q3W monotherapy. All participants had previously received at least one line of prior therapy, and 60.5% had received two or more lines of anticancer treatment.
The confirmed overall objective response rate (ORR) was 23.3%, and progression-free survival (PFS) events occurred in 26 patients, with a median progression-free survival (mPFS) of 5.3 months (4.1-7.4) as of the data cutoff date. (link)
Previously, in May 2024, the CDE has granted IBI343 its first BTD for monotherapy in the treatment of CLDN18.2-positive advanced gastric/gastro-esophageal junction adenocarcinoma (GC) patients who have progressed after at least two lines of prior systematic treatments. In addition, in June 2024, IBI343 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of advanced, unresectable or metastatic PDAC that has relapsed and/or is refractory to one prior line of therapy. The first patient in the U.S. Phase 1 study of IBI343 was successfully dosed in December 2024.

Dr. Hui Zhou, Senior Vice President of Innovent, said, "Pancreatic cancer is an aggressive and difficult-to-diagnose malignancy. At present, treatment for advanced pancreatic cancer relies primarily on systemic chemotherapy, with particularly limited options for second-line treatment. This results in poor patient outcomes and underscores an urgent unmet clinical need. As the world’s first CLDN18.2 ADC to receive BTD in this difficult-to-treat cancer, IBI343 monotherapy has shown encouraging efficacy and tolerable safety in late-line treatment of patients with advanced pancreatic cancer. Subject to PoC data readout, we plan to initiate pivotal MRCT studies to further confirm its efficacy and safety in this indication. Additionally, we will also explore the potential of IBI343 in combination therapy for pancreatic cancer and other solid tumors, including gastric cancer."

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of investigational drugs for serious diseases or conditions when preliminary clinical evidence indicates substantial improvement over current therapies. BTD qualifies a drug candidate for accelerated review by the CDE and provides the sponsor with timely advice and communication to expedite the approval process, helping to address the unmet clinical needs of patients more swiftly.

About Pancreatic Ductal Adenocarcinoma

Pancreatic cancer is one of the most aggressive malignances of the digestive system, with a 5-year survival rate of about 10%[i]. Despite rising incidence rates in recent years, early detection remains low, seriously endangering human life and health. Current treatment for advanced pancreatic cancer is primarily based on systemic chemotherapy, with first-line treatment options typically including fluorouracil (5-FU) or gemcitabine-based chemotherapy. However, second-line treatment options are limited, offering a chemotherapy response rate of only 6-16%, a median progression free survival of 2 to 5 months, and a median overall survival of approximately 6 to 9 months[ii]. These statistics highlight the urgent need for new therapeutic approaches.

Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally confined to the gastric mucosa. The development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells[iii]. CLDN18.2 is present in 50% to 70% of pancreatic cancer cases, making it a highly targeted biomarker for therapeutic development[iv].

About IBI343 (CLDN18.2 ADC)

IBI343 is an antibody-drug conjugate composed of an anti-CLDN18.2 antibody, and a cytotoxic drug exatecan. Binding of IBI343 to CLDN18.2-expressing tumor cells results in CLDN18.2-dependent internalization of IBI343. Degradation of the cleavable linker will release the drug that causes DNA damage, leading to apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring tumor cells, resulting in a strong "bystander killing effect" of IBI343. As an innovative TOPO1i ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in Phase 1 clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric and pancreatic cancers, including a Phase 3 trial (NCT06238843) for GC and a multi-regional Phase 1 trial (NCT05458219) for PDAC ongoing.

IBI343 was granted breakthrough therapy designation (BTD) by China’s National Medical Products Administration (NMPA) for two indications, as monotherapy in patients with CLDN18.2–positive GC who progressed after two prior lines of systemic treatment, and in patients with CLDN18.2-positive PDAC who have progressed after at least one line of prior systematic treatment. IBI343 also received Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of advanced unresectable or metastatic PDAC that has relapsed and/or is refractory to one prior line of therapy.

On January 15, 2025 Johnson & Johnson (NYSE: JNJ) reported that it has initiated the submission of an original New Drug Application with the U.S. Food and Drug Administration (FDA) for TAR-200 for the treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ (CIS), with or without papillary tumors (Press release, Johnson & Johnson, JAN 15, 2025, View Source [SID1234649748]). This submission is being reviewed by the FDA through the Real-Time Oncology Review (RTOR) program, which allows the FDA to review data before the complete application is formally submitted and helps ensure treatments are available for patients as soon as possible.

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"Upon approval, TAR-200 promises to be a meaningful additional treatment option for certain patients with NMIBC, addressing a critical need for people who have had relatively limited therapeutic alternatives. Many patients face life-altering surgical options such as radical cystectomy, which is complete bladder removal," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Head, Oncology, Johnson & Johnson Innovative Medicine. "By combining our expertise in innovative medicine and medical devices, Johnson & Johnson is uniquely positioned to transform how we treat certain types of bladder cancer through the first and only intravesical drug releasing system for this disease. We look forward to working with the FDA in review of this application."

The submission of this innovative intravesical drug releasing system is supported by data from the Phase 2b SunRISe-1 registration study. Data collected through the second quarter of 2024 and presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 Congress as a late-breaking oral presentation showed an 83.5 percent complete response (CR) rate and highly durable CRs without the need for reinduction – at a median follow-up of nine months, 82 percent of responders maintained response. At data cutoff in May 2024, safety and tolerability data presented at ESMO (Free ESMO Whitepaper) demonstrated a low occurrence of Grade 3 or higher treatment-related adverse events (TRAEs) (9 percent); five patients had TRAEs leading to discontinuation (6 percent) and no treatment-related deaths were reported.1

TAR-200 is an investigational intravesical drug releasing system designed to provide sustained local delivery of gemcitabine into the bladder. It is placed into the bladder by a healthcare professional using a co-packaged urinary placement catheter in an outpatient setting in under five minutes and without the need for anesthesia.

In December 2023, the FDA granted Breakthrough Therapy Designation (BTD) to TAR-200 for the treatment of adult patients with BCG-unresponsive HR-NMIBC with CIS who are ineligible for or have elected not to undergo radical cystectomy.

About SunRISe-1, Cohort 2
SunRISe-1 (NCT04640623), Cohort 2, is a randomized, parallel-assignment, open-label Phase 2b clinical study evaluating the safety and efficacy of TAR-200 monotherapy alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients who are ineligible for, or elected not to undergo, radical cystectomy. The primary endpoint for Cohort 2 is CR rate at any time point. Secondary endpoints include duration of response (DOR), overall survival (OS), pharmacokinetics, quality of life, safety and tolerability.

About High-Risk Non-Muscle-Invasive Bladder Cancer
High-risk non-muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer compared to low-risk NMIBC.2, 3 HR-NMIBC makes up 15-44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS. Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.4, 5 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.6 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.

On January 15, 2025 Chromatin Bioscience reported its ongoing collaboration with EsoBiotec, which has successfully advanced its ESO-T01 in vivo CAR-T candidate into clinical trials (Press release, EsoBiotec, JAN 15, 2025, View Source [SID1234649749]). ESO-T01 is the first in vivo B-cell maturation antigen (BCMA) CAR-T candidate to reach the clinical stage and utilises a synthetic promoter designed using Chromatin Bio’s proprietary promoter design platform, chromatinLENS, exclusively for EsoBiotec as part of its innovative approach to immunotherapy.

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EsoBiotec’s ESO-T01, developed using its ENaBL platform, is a T cell targeted lentiviral vector expressing a BCMA-targeted CAR construct for the treatment of multiple myeloma. This construct is regulated by a Treg-specific synthetic promoter developed in collaboration with Chromatin Bioscience. Early studies demonstrated highly effective in vivo transduction, with the BCMA CAR transgene expressed specifically in T cells, leading to the generation of a large population of circulating BCMA CAR-T cells that persisted throughout the study. These results highlight the long-term durability and efficacy of the engineered T cells, marking an important milestone for the therapeutic.

"ESO-T01 is the first in vivo BCMA CAR-T candidate to advance to the clinical stage, showcasing the capabilities of our ENaBL platform technology that reprograms immune cells within the body to combat cancer," stated EsoBiotec CEO Jean-Pierre Latere, Ph.D. "While various treatments exist for multiple myeloma, including ex vivo CAR-T options, many come with severe side effects and are limited by manufacturing capacity, logistical challenges, and high costs. We are excited to collaborate with Chromatin Bioscience to integrate this innovative synthetic promoter, aiming to enhance the safety and efficacy profile of ESO-T01."

Chromatin Bioscience’s chromatinLENS platform allows for the identification of highly specific, cell-type selective gene regulatory elements from the dark genome, offering significant advantages in minimising off-target effects while ensuring robust and durable therapeutic efficacy. These promoters are critical in ensuring the success of advanced therapies like ESO-T01, where targeted expression in T cells is paramount for the safety and efficacy of the treatment.

"EsoBiotec’s progress to the clinic is an exciting development in the field of gene therapy," said Michael Roberts, CEO and Founder of Chromatin Bioscience. "Our synthetic promoters are designed to provide precision and durability in gene expression, and we are pleased that they are playing a role in ensuring the success of ESO-T01. This collaboration represents the power of combining cutting-edge gene therapy with targeted gene expression technologies to offer new treatment options for patients."

On January 14, 2025 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that it will present its 2025 strategic priorities and progress on the Company’s pipeline of mRNA therapeutics, immunomodulators, and targeted therapies at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco, California (Press release, BioNTech, JAN 14, 2025, View Source [SID1234649700]).

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"We aim to develop BioNTech into a global immunotherapy powerhouse with the potential to improve the standard of care with innovative oncology products and prophylactic vaccines against infectious diseases​. In oncology, we are focused on addressing the full spectrum of solid tumors with investigational combination therapies in two pan-tumor technology pillars: our mRNA-based cancer immunotherapies for the early, adjuvant setting, and our differentiated anti-PD-L1/-VEGF-A bispecific antibody candidate BNT327/PM8002 for the treatment of advanced cancers. With our capabilities, we believe BioNTech is uniquely positioned to develop personalized, yet scalable cancer treatments based on mRNA," said Prof. Ugur Sahin, M.D., Co-Founder and Chief Executive Officer of BioNTech. "2025 is an important year, with data updates expected across both pillars and additional global clinical trial starts planned to generate evidence on our combination treatment concepts."

Prof. Ugur Sahin, M.D., will present strategic priorities and a pipeline update at the conference on Tuesday, January 14, 2025, at 6:00 p.m. CET/ 12:00 p.m. EST. A live webcast of the presentation will be available on the "Events & Presentations" page in the investor relations section on the Company’s website. A replay of the webcast will be archived on the Company’s website for 30 days following the conference.

Summary of selected pipeline updates

BNT327/ PM8002, an investigational bispecific antibody combining PD-L1 checkpoint inhibition with VEGF-A neutralization being developed in collaboration with Biotheus:

In December 2024, BioNTech initiated a global randomized Phase 3 clinical trial (NCT06712355) evaluating BNT327/PM8002 plus chemotherapy compared to atezolizumab plus chemotherapy in first line extensive-stage small cell lung cancer ("ES-SCLC").
In December 2024, BioNTech initiated a global randomized Phase 2/3 clinical trial (NCT06712316) evaluating BNT327/PM8002 plus chemotherapy compared to pembrolizumab and chemotherapy in first line NSCLC.
A global randomized Phase 3 clinical trial evaluating BNT327/PM8002 in first line triple-negative breast cancer ("TNBC") is on track to start in 2025.
Plan to initiate additional clinical trials exploring novel combinations of BNT327/PM8002 with ADCs BNT323/DB-1303 (trastuzumab pamirtecan), BNT324/DB-1311 and BNT326/YL202 in 2025.
Plan to present first clinical data from the ongoing global Phase 1/2 expansion cohorts (NCT05438329) evaluating BNT327/PM8002 plus BNT325/DB-1305 in multiple solid tumors in 2025.
Plan to present clinical data from the ongoing global Phase 2 dose optimization trials evaluating BNT327/PM8002 plus chemotherapy in advanced TNBC (NCT06449222) and first line SCLC (NCT06449209) in 2025.
Autogene cevumeran (BNT122/RO7198457), an investigational mRNA cancer immunotherapy based on an individualized neoantigen-specific immunotherapy ("iNeST") approach being developed in collaboration with Genentech Inc. ("Genentech"), a member of the Roche Group:

In December 2024, the first patient was treated in a global randomized Phase 2 clinical trial (IMCODE004) (NCT06534983) evaluating autogene cevumeran in combination with nivolumab compared to nivolumab alone in high-risk muscle-invasive urothelial carcinoma ("MIUC").
Interim data from an ongoing global randomized Phase 2 clinical trial (NCT04486378) evaluating autogene cevumeran compared to watchful waiting in adjuvant ctDNA+ stage II (high risk) / stage III colorectal cancer ("CRC") are anticipated in late 2025 or 2026.
BNT323/DB-1303 (trastuzumab pamirtecan), an investigational HER2-targeted ADC being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. ("DualityBio"):

Plan to present clinical data from an ongoing Phase 1/2a trial (NCT05150691) evaluating BNT323/DB-1303 in HER2-expressing advanced endometrial cancer in 2025.
Preparation of a potential Biologics License Application ("BLA") submission for BNT323/DB-1303 as a second line or subsequent therapy in HER2-expressing advanced endometrial cancer​ in 2025.
Plan to initiate a global Phase 3 confirmatory clinical trial (NCT06340568) evaluating BNT323/DB-1303 in advanced endometrial cancer in 2025.
COVID-19 vaccine and other candidates

For 2025, BioNTech and Pfizer Inc. ("Pfizer") expect largely stable vaccination rates and market share in the U.S. and revenue phasing similar to 2024, primarily concentrated in the back half of the year, with the distribution between Q3 and Q4 dependent on the timing of strain recommendation and approvals by regulatory agencies. Advanced purchase agreements remain in place outside of the U.S., including in the European Union.
BioNTech and Pfizer continue to invest in the research and development of next-generation and combination COVID-19 vaccine candidates.
Upcoming Investor and Analyst Events

Full Year and Fourth Quarter 2024 Financial Results: March 10, 2025
Annual General Meeting: May 16, 2025

On January 14, 2025 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported its anticipated 2025 milestones as it continues its evolution into becoming a fully integrated biotechnology company focused on orally bioavailable degraders (Press release, C4 Therapeutics, JAN 14, 2025, View Source [SID1234649701]).

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"Stellar execution in 2024 has set up 2025 to be a pivotal year for the company as we work to generate important data that will position us to advance programs and bring degrader medicines to patients searching for new therapeutic options," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "The cemsidomide data presented at the ASH (Free ASH Whitepaper) Annual Meeting in December support a potentially best-in-class profile and we are preparing for the next phase of development of this molecule. We continue to progress the CFT1946 Phase 1/2 study and will leverage data from the tumor specific cohorts to determine the development path for this program. In addition, we expect data from the CFT8919 Phase 1 dose escalation study run by our partner Betta Pharmaceuticals in China, which will define its potential for non-small cell lung cancer patients with the EGFR L858R mutation. We are excited about the degrader rationale for these programs, which we believe have the potential to deliver value for patients, caregivers, physicians and shareholders."

ANTICIPATED 2025 MILESTONES

Cemsidomide: Cemsidomide is an oral degrader of IKZF1/3 for the potential treatment of relapsed/refractory (R/R) multiple myeloma (MM) and R/R non-Hodgkin’s lymphoma (NHL).

Multiple Myeloma

Enable initiation of the next phase of clinical development to investigate cemsidomide in combination with dexamethasone in the late-line setting, and in combination with other MM agents for earlier lines of treatment. These new studies are expected to initiate in early 2026.
Complete Phase 1 dose escalation and present data in the second half of 2025.
Non-Hodgkin’s Lymphoma

Complete Phase 1 dose escalation and present data in the second half of 2025.
Open expansion cohort(s) of the current Phase 1/2 trial in patients with peripheral T-cell lymphoma (PTCL) in the second half of 2025.
Enable initiation of the next phase of clinical development to investigate cemsidomide monotherapy in later lines of therapy in PTCL. This new study is expected to initiate in early 2026.
CFT1946: CFT1946 is an oral degrader targeting BRAF V600 mutations for the potential treatment of solid tumors including colorectal cancer (CRC), melanoma and other malignancies with V600 mutations.

Complete monotherapy Phase 1 dose escalation in BRAF V600 mutant solid tumors in the first half of 2025.
Generate data from the Phase 1 cohorts exploring monotherapy CFT1946 in melanoma, CFT1946 in combination with cetuximab in CRC and CFT1946 in combination with trametinib in melanoma. Data from these cohorts will define and enable the next phase of development.
Present Phase 1 data in the second half of 2025. These presentations will include: (1) monotherapy in BRAF V600 mutant solid tumors, (2) monotherapy expansion cohorts in melanoma, and (3) in combination with cetuximab in CRC.
CFT8919: CFT8919 is an oral degrader targeting EGFR bearing an oncogenic L858R mutation for the potential treatment of non-small cell lung cancer (NSCLC).

Evaluate data from the Phase 1 dose escalation study in Greater China, which is led by partner Betta Pharmaceuticals, in patients with locally or advanced metastatic NSCLC harboring an EGFR L858R mutation. These data will be used to determine the next phase of development.
Discovery: C4T will continue to utilize its TORPEDO platform to develop orally bioavailable degraders for oncology and non-oncology targets for internal research and collaboration programs. To further highlight its deep expertise in drug discovery, C4T plans to:

Present and publish preclinical work from its internal pipeline and TORPEDO platform.
Advance internal and collaboration programs to key milestones.
2024 ACCOMPLISHMENTS

Cemsidomide: C4T advanced the Phase 1/2 clinical trial and delivered data reinforcing the potential of cemsidomide to become a backbone therapy of choice in MM and NHL where IKZF1/3 degradation is warranted.

Multiple Myeloma

At ASH (Free ASH Whitepaper), presented data on cemsidomide in combination with dexamethasone. As of the data cutoff date of October 11, 2024, the dose level exploring 75 µg once daily (QD) achieved an overall response rate (ORR) of 36 percent. Cemsidomide was well-tolerated across all dose levels.
The maximum tolerated dose has not yet been reached. Patients are enrolling in the 100 µg QD cohort.
Non-Hodgkin’s Lymphoma

At ASH (Free ASH Whitepaper), presented data on cemsidomide monotherapy. As of the data cutoff date of October 11, 2024, cemsidomide demonstrated a 38 percent ORR across all subtypes and doses studied. In PTCL, cemsidomide achieved a 44 percent ORR and a 25 percent complete metabolic response rate.
The maximum tolerated dose has not yet been reached. Patients are enrolling in the 75 µg QD cohort.
CFT1946: C4T advanced the Phase 1/2 clinical trial across multiple arms and delivered monotherapy data demonstrating proof of mechanism and early evidence of proof of concept.

At the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, presented monotherapy data demonstrating CFT1946 is well tolerated across all dose levels and demonstrates initial signs of anti-tumor activity across all dose levels.
At the TPD Summit, presented new preclinical data demonstrating CFT1946 has the ability to cross the blood-brain barrier, with Kpu,u values in the range of 0.34 to 0.88.
Progressed the Phase 1 monotherapy dose escalation study. Began enrolling patients across multiple exploratory cohorts: CFT1946 monotherapy in melanoma, CFT1946 in combination with trametinib in melanoma, and CFT1946 in combination with cetuximab in CRC.
CFT8919: Betta Pharmaceuticals, with C4T support, initiated the Phase 1 clinical trial of CFT8919 in Greater China.

Discovery: C4T further validated its TORPEDO platform and advanced key research efforts.

Delivered two development candidates for non-oncology targets to collaborator Biogen.
Established a new collaboration with Merck KGaA, Darmstadt, Germany focused on two critical oncogenic proteins.
Continued to progress its internal discovery portfolio of orally bioavailable degraders.
Corporate: C4T further strengthened its leadership across its management team and Board of Directors to supports its evolution into a fully integrated biotechnology company.

Paige Mahaney, Ph.D., was appointed chief scientific officer. Dr. Mahaney is an experienced drug developer who has helped leading pharmaceutical companies build clinical portfolios across a wide range of disease indications and treatment modalities.
C4T continued to evolve its governance by appointing three new members to its Board of Directors who bring deep experience across drug discovery, commercialization and lifecycle management.
Cash Guidance
C4T expects that its cash, cash equivalents and marketable securities as of December 31, 2024, together with anticipated collaboration expense reimbursements, but excluding any collaboration option or milestone payments, will enable the company to fund its operating plan into 2027.

JP Morgan Presentation
C4T will present at the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15, 2025 at 2:15 pm PST (5:15 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.