On May 8, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported financial results for the first quarter ended March 31, 2024, as well as recent business highlights (Press release, Catalent, MAY 8, 2024, https://www.catalent.com/catalent-news/siren-biotechnology-and-catalent-enter-partnership-for-manufacturing-of-aav-gene-therapies-for-cancer/ [SID1234642851]).

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"We are off to a strong start in 2024 with enrollment progressing well in our ongoing Phase 1/2 trials of CFT7455, now known as cemsidomide, and CFT1946. We look forward to maintaining this momentum and are on track for clinical readouts from both trials in the second half of the year," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "During the first quarter, we continued to leverage our discovery expertise as we entered into a new license and collaboration agreement with Merck KGaA, Darmstadt, Germany and delivered our first development candidate to Biogen. Together, these accomplishments further validate the excitement around our TORPEDO platform and our ability to design innovative molecules for a range of diseases where degraders have the potential to become new therapeutic options for patients searching for treatments."

FIRST QUARTER 2024 AND RECENT ACHIEVEMENTS
Cemsidomide (CFT7455): Cemsidomide (CFT7455) 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 lymphomas (NHL).
•Advanced the Phase 1/2 Clinical Trial. The dose escalation portion of the Phase 1/2 trial evaluating cemsidomide (CFT7455) in combination with dexamethasone for R/R MM and as a monotherapy for R/R NHL continues to enroll patients. For the combination with dexamethasone MM arm, the 62.5 µg dose has been declared safe and patients are enrolling at a higher dose level. Simultaneously, additional patients are enrolling in the 62.5 µg expansion cohort. For the monotherapy NHL arm, the 62.5 µg cohort has been declared safe and patients are enrolling at a higher dose level.
CFT1946: CFT1946 is an oral degrader targeting BRAF V600X mutations for the potential treatment of solid tumors including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and melanoma.

•Advanced the Phase 1/2 Clinical Trial. The dose escalation portion of the CFT1946 Phase 1/2 trial for BRAF V600X mutations, including NSCLC, CRC and melanoma, continues to enroll patients. The 320 mg dose has been declared safe and patients are enrolling at a higher dose level. Simultaneously, additional patients are enrolling at the 160 mg and 320 mg dose levels for pharmacokinetic, pharmacodynamic and anti-tumor activity evaluation.
•Presented New Preclinical Data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024. In April 2024, C4T presented preclinical data highlighting superior activity of CFT1946 compared to BRAF inhibitor standard of care combinations in models of BRAF V600X NSCLC, CRC, melanoma and brain metastasis.
•Trial-in-Progress Poster Accepted at European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) Gastrointestinal (GI) Cancers Congress 2024. C4T will present a trial-in-progress poster on the CRC opportunity within the ongoing CFT1946 Phase 1/2 trial at ESMO (Free ESMO Whitepaper) GI 2024, taking place from June 26 to June 29, 2024.
Collaborations:
•Delivered development candidate to Biogen. In April 2024, C4T earned an $8 million payment after Biogen accepted delivery of a development candidate in an undisclosed indication. Biogen is responsible for all future clinical development and commercialization for this program.
•License and collaboration agreement with Merck KGaA, Darmstadt, Germany (MKDG). In March 2024, C4T entered into a license and collaboration agreement with MKDG to exclusively discover two targeted protein degraders against critical oncogenic proteins that C4T has progressed within its internal discovery pipeline. Under the terms of the agreement, C4T received an upfront payment of $16 million. MKDG will fund C4T’s discovery research efforts. C4T has the potential to receive up to approximately $740 million in discovery, regulatory and commercial milestone payments across the collaboration. In addition, C4T is eligible for mid-single to low-double digit tiered royalties on future sales for each program.

CORPORATE UPDATES
•In April 2024, Dan Powers, DO, was appointed as senior vice president, clinical development. Dr. Powers brings over 20 years of leadership experience in clinical development and medical affairs within the hematology and solid tumor space. Dr. Powers reports to C4T’s chief medical officer, Len Reyno, M.D., and is responsible for leading clinical development programs as well as supporting and executing our ongoing clinical studies.

KEY UPCOMING MILESTONES
Cemsidomide (CFT7455):
•Present updated data from the ongoing Phase 1 dose escalation trial in R/R MM in 2H 2024.
•Present data from the ongoing Phase 1 dose escalation trial in R/R NHL in 2H 2024.
•Complete Phase 1 dose exploration in R/R MM and R/R NHL by year-end 2024.
CFT1946:
•Present data from the ongoing Phase 1 monotherapy dose escalation trial in NSCLC, CRC, melanoma and other cancers with BRAF V600X mutations in 2H 2024.

FIRST QUARTER 2024 FINANCIAL RESULTS

Revenue: Total revenue for the first quarter of 2024 was $3.0 million, compared to $3.8 million for the first quarter of 2023. The decrease in revenue was primarily due to the Biogen and Calico research terms ending in 2023. In 2024, we commenced work on our new collaboration agreements with Merck Sharp & Dohme LLC (Merck) and MKDG, which were signed in December 2023 and March 2024, respectively. Total revenue for the first quarter of 2024 reflects revenue recognized under our collaborations with MKDG, Merck, Roche and Biogen, and total revenue recognized in the first quarter of 2023 reflects revenue recognized under collaboration agreements with Roche, Biogen and Calico.

Research and Development (R&D) Expense: R&D expense, net of a one-time $1.9 million restructuring charge, was $22.5 million for the first quarter of 2024. This is compared to $29.0 million for the first quarter of 2023. The reduction in R&D expense was primarily due to the prioritization of our internal discovery efforts and stopping clinical development for CFT8634, partially offset by increased clinical trial expense as cemsidomide (CFT7455) and CFT1946 continue to advance.

General and Administrative (G&A) Expense: G&A expense, net of a one-time $0.5 million restructuring charge, was $10.3 million for the first quarter of 2024. This is compared to $10.9 million for the first quarter of 2023. The nominal decrease in G&A expense was primarily attributable to a reduction in external consulting spend.
Net Loss and Net Loss per Share: Net loss for the first quarter of 2024 was $28.4 million, compared to $34.8 million for the first quarter of 2023. Net loss per share for the first quarter of 2024 was $0.41 compared to $0.71 for the first quarter of 2023.

Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of March 31, 2024 were $299.2 million, compared to $281.7 million as of December 31, 2023. The increase was primarily the result of proceeds received in January 2024 from the sale of shares of our common stock to a subsidiary of our partner Betta Pharmaceuticals and proceeds from settlement of shares under our at the market (ATM) offering arrangement, both of which were previously disclosed. These inflows were partially offset by cash used in operating activities. C4T expects that its cash, cash equivalents and marketable securities as of March 31, 2024 will be sufficient to fund planned operating expenses and capital expenditures into 2027.

On May 7, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519), National Cancer Center Hospital (hereafter, NCCH), Osaka Medical and Pharmaceutical University (hereafter, OMPU) and MICIN reported introduction of a new decentralized clinical trial (DCT)* structure and the start of DCT in a Chugai-sponsored phase I clinical trial for patients with advanced solid tumors (Press release, Chugai, MAY 8, 2024, View Source;category= [SID1234642809]). NCCH and OMPU will collaborate using telemedicine as the primary institution and the satellite institution,** respectively, and some tests and assessments that were conventionally performed at institutions will be performed at the satellite institution.

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This is the first study in Japan to utilize a satellite institution for a company-sponsored phase I clinical trial in oncology. Since the number of institutions is very limited in phase I clinical trials, it is expected to improve access to clinical trials of new drug candidates for patients living far from institutions. We will evaluate this new DCT structure, with the aim of building an implementation structure that provides access to clinical trials for many patients regardless of where they live.

[Background and details]
Since clinical trials of new drug candidates are conducted at a limited number of medical institutions, some patients living far from the institution give up their participation in the clinical trial due to the time and financial burden associated with in-person visits. Establishing an environment that improves the patients’ access to clinical trials is a common challenge in clinical development, including pharmaceutical companies and academias.1 A retrospective study conducted at NCCH also showed that the participation rate in clinical trials tended to decrease for patients with travel time of 120 minutes or more.2 In addition, in phase I clinical trials evaluating drug safety for cancer patients, it is necessary to closely monitor patients’ condition while ensuring the patients’ safety. Therefore, there are few medical institutions where phase I clinical trials can be conducted.

DCTs, which are not dependent on in-person visits, have been attracted attention as a new approach in recent years. In Japan, some guidelines have been issued, and DCT is gradually being introduced into clinical trials, but the use in the oncology area is still limited.

This is a Chugai-sponsored phase I clinical trial for patients with advanced solid tumors, conducted with NCCH as a primary institution and OMPU as a satellite institution. Since the travel time from OMPU to NCCH exceeds 120 minutes, DCT is expected to reduce patients’ burdens. Patients will be able to visit the satellite institution instead of the primary institution to receive some tests and assessments for this clinical trial via telemedicine. The DCT platform MiROHA, provided by MICIN, will also be utilized for telemedicine visits and for obtaining remote re-consent using eConsent.

Improving access for patients is a common challenge in the pharmaceutical industry because clinical trials of new drug candidates are conducted at a limited number of medical institutions. The utilization of satellite institutions is expected to reduce the burden on patients and improve access to clinical trials. Chugai’s most prioritized value is patient-centricity. We will develop new drugs together with patients as partners, with the aim of realizing advanced and sustainable patientcentric healthcare.
Dr. Osamu Okuda, President and CEO, Chugai Pharmaceutical Co., Ltd.

To patients living in remote areas, access to clinical trials is drastically reduced, especially true for rare cancers and those of rare fractions, which trials are concentrated in hospitals in urban centers. By removing the need for patients to commute long hours, DCTs can address this issue. With new means, our team will reinvigorate drug development in Japan, delivering treatments expeditiously to patients nationwide, which is our mission.
Dr. Yasuyuki Seto, Director of National Cancer Center Hospital

In the phase I clinical trial for solid tumors, our institution will play a role as a satellite institution, contributing to the implementation of "no one left behind in cancer care" practices. In the face of disparities in access to clinical trials and information, particularly in rural areas, we have established a decentralized clinical trial system aimed at reducing the burden on patients while addressing these disparities. We have experience in many phase I trials of new anti-cancer drugs, and we are committed to the success of this challenging trial and will endeavor to ensure the realization of cancer patients’ "Well Being" even in rural regions.
Dr. Takahiro Katsumata, Osaka Medical and Pharmaceutical University Hospital

It is hoped that this trial initiative, which utilizes satellite medical institutions, will reduce the burden on patients and expand their options for participating in clinical trials.
As a leading DCT company, we are committed to contributing to a new way of conducting clinical trials through this new attempt.
Dr. Seigo Hara, MICIN, Inc., Representative CEO

On May 8, 2024 Corvus Pharmaceuticals, Inc. reported its first quarter 2024 results (Press release, Corvus Pharmaceuticals, MAY 8, 2024, View Source [SID1234642791]).

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On May 7, 2024 Alltrna, a Flagship Pioneering company unlocking transfer RNA (tRNA) biology and pioneering tRNA therapeutics to regulate the protein universe and resolve disease, reported the presentation of new data at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting demonstrating that Alltrna’s platform, enabled by machine learning (ML), can optimize sequences and modifications from natural tRNAs to significantly increase in vivo activity to readthrough premature termination codons (PTCs) caused by nonsense mutations (Press release, Alltrna, MAY 7, 2024, https://www.alltrna.com/press/alltrna-applies-machine-learning-to-engineer-trna-oligonucleotides-with-significantly-improved-activity-and-demonstrates-in-vivo-readthrough-of-the-two-most-common-premature-termination-codons-in-genetic-disease [SID1234646024]).

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"Alltrna’s ML-driven platform explores at an unprecedented scale the expansive combinatorial space of tRNA sequences and modifications, which has the potential to generate more engineered tRNA oligonucleotides than atoms in the universe," said Michelle C. Werner, CEO of Alltrna. "The data demonstrate the power of Alltrna’s platform to identify key combinations of tRNA sequences and modifications and precisely design tRNA oligonucleotides with significantly improved in vivo activity. With optimized engineered tRNAs for the two most prevalent premature termination codons, we are advancing preclinical studies for our first Stop Codon Disease indications."

tRNAs are programmable molecules with a diverse biology of sequences and modifications that are key to their structure, function, and stability. There’s the potential for approximately 10^34 tRNA sequences and more than 120 natural and synthetic modifications for each nucleotide. Using ML-powered screens, Alltrna scientists applied high-throughput sequence optimization to increase engineered tRNA activity by ~100-fold. ML-driven modification optimization further increased engineered tRNA activity.

Data were presented for the optimization of engineered tRNA oligonucleotides to address two different PTCs: Arg-TGA and Gln-TAG. Delivered using a liver-directed lipid nanoparticle (LNP), both optimized tRNAs showed robust in vivo activity in two transgenic mouse models. The first carries a human rare disease gene with a PTC mutation, the second carries a reporter gene with a different PTC as a general in vivo model for Stop Codon Disease. Alltrna previously presented in vitro data on the engineered tRNA for Arg-TGA showing that it can readthrough nonsense mutations regardless of gene or location in 25 disease reporter models, 14 different genes, and seven different mutation locations on a single gene.

"These data confirm that the application of high-throughput sequence and ML-driven modification optimization through Alltrna’s unique platform can significantly increase the in vivo activity of engineered tRNAs," said Stephen W. Eichhorn, Ph.D., Head of Computational and Molecular Biology at Alltrna. "We’ve also demonstrated that we can engineer robust tRNA activity for two different premature termination codons, each of which are highly prevalent in Stop Codon Disease."

About Stop Codon Disease

Stop Codon Disease encompasses thousands of rare and common diseases that stem from premature termination codons (PTC) also called nonsense mutations, where the code for an amino acid has been mutated into a premature "stop" codon. This results in a truncated or shortened protein product with no or altered biological activity that causes disease. Approximately 10% of all people with a genetic disease have Stop Codon Disease, representing approximately 30 million people worldwide. Alltrna is engineering tRNA medicines that can read these PTC mutations and deliver the desired amino acid, thereby restoring the production of the full-length protein.

On May 7, 2024 Kyowa Hakko Kirin reported its Consolidated Financial Summary (IFRS) Fiscal 2024 First Quarter (Press release, Kyowa Hakko Kirin, MAY 7, 2024, View Source [SID1234645288]).

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