On November 6, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported its partner Betta Pharmaceuticals has dosed the first patient in the Phase 1 clinical trial of CFT8919, an orally bioavailable allosteric degrader of EGFR L858R for non-small cell lung cancer (NSCLC), in Greater China (Press release, C4 Therapeutics, NOV 6, 2024, View Source [SID1234648576]).

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"We are pleased to see CFT8919, our fourth small molecule degrader to enter the clinic, begin the journey through clinical development in Greater China with our partner Betta Pharmaceuticals," said Len Reyno, M.D., chief medical officer of C4 Therapeutics. "CFT8919 may offer an exciting advancement in treating non-small cell lung cancer driven by an EGFR mutation, which is currently treated with EGFR tyrosine kinase inhibitors (TKIs) that offer a less durable response for patients with the EGFR L858R driver mutation than those with other driver mutations. We, along with our partner Betta Pharmaceuticals, believe CFT8919 may offer a novel targeted therapy for patients and physicians searching for treatment options."

C4T designed CFT8919 to be potent and selective against EGFR bearing an oncogenic L858R mutation and capable of overcoming common EGFR secondary mutations that render patients refractory to EGFR TKIs. The EGFR mutation is particularly common in NSCLC patients of Asian heritage. In China, where approximately 693,000 patients are diagnosed with NSCLC annually, approximately 50 percent of diagnoses are driven by the EGFR mutation. The EGFR L858R mutation is the second most common EGFR mutation, found in approximately 40 percent of patients diagnosed with an EGFR mutation in the U.S. and China.

In 2023, C4T and Betta Pharmaceuticals entered into a strategic collaboration to develop, manufacture and commercialize CFT8919 in Greater China, including Hong Kong SAR, Macau SAR and Taiwan. Under the terms of the agreement, C4T is eligible for up to $357 million in potential milestones plus royalties on net sales. C4T retains development and commercialization rights for CFT8919 in the United States, European Union and rest of the world.

About CFT8919
CFT8919 is an orally bioavailable allosteric BiDAC degrader that is designed to be potent and selective against EGFR bearing an oncogenic L858R mutation. In preclinical studies, CFT8919 is active in in vitro and in vivo models of L858R driven non-small cell lung cancer. Importantly, CFT8919 retains full activity against additional EGFR mutations that confer resistance against approved EGFR inhibitors including L858R-C797S, L858R-T790M, and L858R-T790M-C797S.

On November 6, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported financial results for the third quarter ended September 30, 2024, and provided a business update (Press release, Nuvation Bio, NOV 6, 2024, View Source [SID1234647872]).

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David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio, reflected on the quarter and stated: "In the third quarter, we continued to execute on our goal of bringing taletrectinib to people living with ROS1-positive NSCLC as quickly as possible, which has been our focus since we closed the acquisition of AnHeart Therapeutics earlier this year. In October, we completed the rolling submission of our NDA for line agnostic full approval of taletrectinib in advanced ROS1-positive NSCLC, which was supported by the pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies that we presented at ESMO (Free ESMO Whitepaper). We believe that these data – a confirmed objective response rate of 89% and median duration of response approaching four years in the TKI-naïve setting – are the strongest data seen to date in the ROS1 space and increase taletrectinib’s potential to become a best-in-class treatment option. Additionally, we are excited about the momentum of our overall pipeline, including safusidenib, our mutant IDH1 inhibitor for both low- and high-grade diffuse IDH1-mutant glioma, where we plan to make meaningful clinical progress next year, and NUV-1511, our first drug-drug conjugate, which we continue to dose escalate in the clinic."

Recent Pipeline Updates:

Taletrectinib, ROS1 inhibitor: Advanced ROS1+ NSCLC

Completed submission of an NDA for taletrectinib to the U.S. FDA for the treatment of advanced ROS1+ NSCLC (line agnostic) in October, in alignment with feedback from the U.S. FDA as part of a pre-NDA meeting.
Company expects the U.S. FDA to accept its NDA submission for full approval as early as year-end 2024, which, if approved, will allow Nuvation Bio to launch taletrectinib in the U.S. as early as mid-2025.
Taletrectinib is the only ROS1 tyrosine kinase inhibitor (TKI) currently in development that has received Breakthrough Therapy Designation from the U.S. FDA for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC who either have or have not previously been treated with ROS1 TKIs (line agnostic).
Pooled data from the pivotal Phase 2 TRUST-I and TRUST-II studies were presented at the 2024 ESMO (Free ESMO Whitepaper) Congress in September. The pooled analysis supported the Company’s NDA submission for taletrectinib.
Key highlights from the pooled analysis include:
Confirmed objective responses in 89% of taletrectinib-treated patients with advanced ROS1+ NSCLC who were tyrosine kinase inhibitor (TKI)-naïve and 56% of those who were TKI-pretreated in the study.
Taletrectinib demonstrated durable responses and prolonged disease control with long-term follow up; median duration of response (DOR) and median progression-free survival (PFS) in TKI-naïve patients were 44 months and 46 months, respectively.
Taletrectinib’s safety and tolerability profile appeared favorable, including a low treatment discontinuation rate of 7%.
Data from the global, pivotal Phase 2 TRUST-II study were presented at the 2024 World Conference on Lung Cancer in September as part of the press program.
Safusidenib, mIDH1 inhibitor: Diffuse IDH1-mutant glioma

Safusidenib is a potentially best-in-class, novel, oral, brain penetrant inhibitor of mutant IDH1.
Phase 2 study of safusidenib in patients with diffuse IDH1-mutant glioma remains ongoing.
NUV-1511, drug-drug conjugate (DDC): Advanced solid tumors

NUV-1511, the Company’s first clinical-stage DDC, fuses a targeting agent to a widely used chemotherapy agent.
Phase 1/2 dose escalation study of NUV-1511 in patients with various advanced solid tumors remains ongoing.
NUV-868, BD2-selective BET inhibitor: Advanced solid tumors

As previously announced, the Company is evaluating next steps for the NUV-868 program, including further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients.
Corporate Updates:

Appointed Philippe Sauvage as Chief Financial Officer in October. Mr. Sauvage brings over 20 years of global leadership experience in finance, operations, and commercialization within healthcare and biopharmaceutical organizations.
Appointed David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio, as Chairman of the Board of Directors. Additionally, the Company appointed Robert Bazemore as lead independent director.
Third Quarter 2024 Financial Results

As of September 30, 2024, Nuvation Bio had cash, cash equivalents and marketable securities of $549.1 million.

For the three months ended September 30, 2024, research and development expenses were $27.7 million, compared to $18.5 million for the three months ended September 30, 2023. The increase was primarily due to a $6.7 million increase in personnel-related costs driven by the acquisition of AnHeart, stock-based compensation and other benefits, $2.4 million increase in third-party costs related to research services and drug manufacturing as a result of clinical trial expense for taletrectinib and $0.1 million increase in amortization of assembled workforce.

For the three months ended September 30, 2024, general and administrative expenses were $19.6 million, compared to $7.8 million for the three months ended September 30, 2023. The increase was due to a $5.3 million increase in personnel-related costs as a result of the acquisition of AnHeart, $4.2 million increase in sales and marketing expense, $1.8 million increase in professional fees, $0.7 million increase in legal fees, and $0.4 million increase in occupancy expense offset by $0.4 million increase in foreign currency impact and $0.2 million decrease in insurance expense.

For the three months ended September 30, 2024, Nuvation Bio reported a net loss of $41.2 million, or $(0.15) per share. This compares to a net loss of $19.6 million, or $(0.09) per share, for the comparable period in 2023.

About Taletrectinib

Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with advanced ROS1+ NSCLC. Taletrectinib is being evaluated for the treatment of patients with advanced ROS1+ NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study.

Taletrectinib has been granted Orphan Drug Designation by the U.S. FDA for the treatment of patients with ROS1+ NSCLC and other NSCLC indications, and Breakthrough Therapy Designations by both the U.S. FDA and China’s National Medical Products Administration (NMPA) for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC. Based on pooled results of the TRUST-I and TRUST-II clinical studies, Nuvation Bio submitted an NDA for taletrectinib to the U.S. FDA for the treatment of patients with advanced ROS1+ NSCLC (line agnostic, full approval). Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC who either have or have not previously been treated with ROS1 TKIs.

On November 6, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported financial results and operational highlights for the third quarter ended September 30, 2024 (Press release, Adicet Bio, NOV 6, 2024, View Source [SID1234647871]).

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"Our commitment to delivering best-in-class gamma delta 1 T cell therapies for patients battling autoimmune diseases and cancer is reflected in the expansion of our clinical pipeline in the third quarter. We are now investigating ADI-001 across six autoimmune indications to provide potentially transformative curative therapies for these debilitating diseases. Additionally, in the fourth quarter we plan to open enrollment for our Phase 1 trial of ADI-270 in patients with metastatic/advanced clear cell renal cell carcinoma (ccRCC), our first gamma delta 1 CAR T cell therapy for solid tumors. This progress highlights the broad and important potential applications of our gamma delta platform," said Chen Schor, President and Chief Executive Officer. "Looking ahead, we anticipate advancing enrollment in these trials and expect to share preliminary clinical data from both lupus nephritis with ADI-001 and metastatic/advanced ccRCC with ADI-270 in the first half of 2025."

Third Quarter 2024 and Recent Operational Highlights:

Autoimmune diseases

Activated clinical sites in ADI-001 Phase 1 trial in autoimmune diseases. In September 2024, Adicet activated sites for its Phase 1 clinical trial of ADI-001 in autoimmune diseases. The company is exploring the potential of ADI-001 across six indications including LN, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), stiff person syndrome (SPS) and anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis (AAV). The Company opened enrollment for patients with LN in 4Q24 and expects to initiate enrollment for patients with SLE, SSc, IIM, and SPS in 1Q25, and for patients with AAV in 2H25. The Company plans to report preliminary clinical data from the Phase 1 clinical study of ADI-001 in LN in 1H25, and for other autoimmune diseases in 2H25, subject to study site initiation and patient enrollment.
FDA clearance of IND amendment to evaluate ADI-001 in IIM and SPS. In October 2024, Adicet announced that the U.S. Food and Drug Administration (FDA) cleared the Company’s Investigational New Drug (IND) amendment application to evaluate ADI-001 in IIM and SPS as part of the Phase 1 clinical trial in autoimmune diseases.
Presented ADI-001 clinical biomarker data demonstrating robust tissue trafficking and complete B cell depletion in secondary lymphoid tissue. In September 2024, Adicet presented clinical biomarker data from the Phase 1 GLEAN trial of ADI-001 at the 9th Annual CAR-TCR Summit. The data demonstrated robust tissue trafficking resulting in high levels of ADI-001, significant chimeric antigen receptor (CAR) T cell activation, and complete CD19+ B cell depletion in secondary lymphoid tissue. These findings further reinforce ADI-001’s potential as a best-in-class allogeneic cell therapy for autoimmune diseases.
Presentation of ADI-001 clinical data at the American College of Rheumatology (ACR) Convergence 2024. In November 2024, Adicet will present an oral abstract highlighting previously presented ADI-001 clinical biomarker data at ACR Convergence 2024 taking place November 14-19 in Washington, D.C.
Hematologic malignancies and solid tumor indications

ADI-270 Fast Track Designation in metastatic/ advanced ccRCC. In July 2024, Adicet announced that the FDA granted ADI-270 Fast Track Designation for the potential treatment of patients with metastatic/advanced ccRCC who have been treated with an immune checkpoint inhibitor and a vascular endothelial growth factor inhibitor.
Presented ADI-270 data at the American Society of Gene & Cell Therapy’s (ASGCT) (Free ASGCT Whitepaper) 2024 Advancing Gene + Cell Therapies for Cancer conference. In October 2024, Adicet presented ADI-270 data in an oral presentation at the ASGCT (Free ASGCT Whitepaper) 2024 Advancing Gene and Cell Therapies for Cancer conference.
Corporate Updates

Appointed Lloyd Klickstein, M.D., Ph.D. to Board of Directors. In August 2024, Adicet appointed Dr. Lloyd Klickstein to its Board of Directors. Dr. Klickstein brings over two decades of leadership experience in the biopharmaceutical industry and biomedical research, and expertise in rheumatology and immunology to Adicet. Dr. Klickstein currently serves as President and Chief Executive Officer of Koslapp Therapeutics, Inc. and is the Board Chair of the Lupus Foundation of New England.
Financial Results for Third Quarter 2024:

Research and Development (R&D) Expenses: R&D expenses were $26.3 million for the three months ended September 30, 2024, compared to $26.2 million during the same period in 2023. The increase in R&D expenses was primarily due to a $0.9 million increase in laboratory expenses, a $0.8 million increase in payroll and personnel expenses as well as a less than $0.1 million increase in professional fees for the period. This increase was partially offset by a $1.3 million decrease in expenses related to contract development manufacturing organizations and other externally conducted research and development and a $0.4 million decrease in allocated facility expenses.
General and Administrative (G&A) Expenses: G&A expenses were $6.9 million for the three months ended September 30, 2024, compared to $6.6 million during the same period in 2023. The increase in general and administrative expenses was primarily due to a $0.3 million increase in payroll and personnel expenses.
Net Loss: Net loss for the three months ended September 30, 2024 was $30.5 million, or a net loss of $0.34 per basic and diluted share, including non-cash stock-based compensation expense of $6.8 million, as compared to a net loss of $49.9 million, or a net loss of $1.16 per basic and diluted share, including non-cash goodwill impairment expense of $19.5 million and non-cash stock-based compensation expense of $5.6 million during the same period in 2023.
Cash Position: Cash, cash equivalents and short-term investments in treasury securities were $202.1 million as of September 30, 2024, compared to $159.7 million as of December 31, 2023. The Company expects that current cash, cash equivalents and short-term investments as of September 30, 2024, will be sufficient to fund its operating expenses into the second half of 2026.

On November 6, 2024 Affini-T Therapeutics, Inc., a clinical stage biopharmaceutical company focused on the development of precision immunotherapies for treatment of patients with solid tumors, reported that a Trial-In-Progress poster for the Company’s Phase 1 clinical trial evaluating AFNT-211 targeting KRAS G12V will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting held in Houston, TX, November 6-10 (Press release, Affini-T Therapeutics, NOV 6, 2024, View Source [SID1234647870]). The team will present three additional posters with preclinical data from its non-viral TRAC-knocked-in T cell therapy targeting TP53-R175H and bi-specific T cell engager programs targeting TP53-R175H, KRAS G12D and KRAS G12V.

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"We are going after cancers with tumor driver mutations like KRAS," said Dirk Nagorsen, M.D., Chief Medical Officer, Affini-T Therapeutics. "Our two clinical stage programs, AFNT-111 and AFNT-211, are specifically designed to leverage precision immunotherapy and synthetic biology approaches to target oncogenic driver mutation KRAS G12V in HLA-A*11:01-positive patients. We started treating patients across these trials earlier this year and we continue to advance these programs through Phase 1."

"Our mission is to address the significant unmet needs of patients with hard-to-treat solid tumors by advancing precision engineered T cell and bispecific T cell engager immunotherapies that target oncogenic driver mutations," said Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics. "We believe that our non-viral multi-kilobase size gene targeted knock-in platform, THRIVETM, will enable us to cost-effectively engineer safe and effective T cell therapy products. We look forward to presenting new preclinical data for THRIVETM-engineered TP53 R175H-targeting TCR T cells (AFNT-313). We will also be disclosing, for the first time, preclinical data for T cell engagers targeting TP53 R175H and KRAS G12V/D mutations from Affini-T’s TETHERTM bispecific platform."

Poster presentation details are as follows:

Title: A Phase 1 Study of Autologous CD4+ and CD8+ T Cells, HLA-A*11:01-restricted, KRAS G12V-specific, Transgenic TCR; CD8α/β Coreceptor and a FAS41BB Switch Receptor in Patients with Solid Tumors
Abstract #662, Primary Category: Clinical Trials in Progress
Presenting Author: Soumit Basu, M.D., Senior Medical Director, Clinical Development, Affini-T Therapeutics
Session Date/Time: Saturday, November 9, 2024, 12:15 PM – 1:45 PM CST and 7:10 PM – 8:30 PM CST

Title: A Non-Virally Engineered T Cell Therapy Targeting the Hotspot Mutation R175H in TP53 with Signals 1, 2, and 3 (TCR, Co-stimulation, and Cytokine) Drives a Coordinated Antitumor CD4/8 T Cell Response
Abstract #393, Primary Category: Cellular Therapies
Presenting Author: Santosh Narayan, Ph.D., Senior Scientist, Immunology & Gene Editing, Affini-T Therapeutics
Session Dates/Times: Immune Engineering Workshop, Thursday, November 7, 2024, 3:10 PM – 5:00 PM CST and Annual Meeting, Friday, November 8, 2024, 12:15 PM – 1:45 PM CST and 5:30 PM – 7:00 PM CST

Title: T Cell Engagers Targeting HLA-A*11:01 KRAS-G12D and KRAS-G12V Mutations for Cancer Immunotherapy
Abstract #1066, Primary Category: Immuno-Conjugates and Chimeric Molecules
Presenting Author: Mark Ng, MS, Senior Scientist II, TCR Discovery, Affini-T Therapeutics
Session Dates/Times: Immune Engineering Workshop, Thursday, November 7, 2024, 3:10 PM – 5:00 PM CST and Annual Meeting, Saturday, November 9, 2024, 12:15 PM – 1:45 PM CST and 7:10 PM – 8:30 PM CST

Title: A Novel T Cell Engager Targeting HLA-A*02:01 TP53-R175H for Cancer Immunotherapy
Abstract #1315, Primary Category: Novel Single-Agent Immunotherapies
Presenting Author: Mark Ng, MS, Senior Scientist II, TCR Discovery, Affini-T Therapeutics
Session Dates/Times: Immune Engineering Workshop, Thursday, November 7, 2024, 3:10 PM – 5:00 PM CST and Annual Meeting, Friday, November 8, 2024, 12:15 PM – 1:45 PM CST and 5:30 PM – 7:00 PM CST

About AFNT-211

AFNT-211 is an investigational autologous T cell therapy that is being administered to patients for the first time. AFNT-211 is currently being evaluated in a Phase 1 clinical trial open to adult patients with solid tumors who have a KRAS G12V mutation. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov, NCT06105021.

On November 6, 2024 Immunomic Therapeutics, Inc., ("ITI"), a privately-held clinical-stage biotechnology company pioneering the study of LAMP-mediated nucleic acid-based immunotherapy reported that it will present at SITC (Free SITC Whitepaper) 39th Annual Meeting 2024 at the George R. Brown Convention Center in Houston, TX on November 8-10, 2024 (Press release, Immunomic Therapeutics, NOV 6, 2024, View Source [SID1234647869]). Associate Director, Vaccine Discovery, Wei Shen, Ph.D., will present a poster entitled, "A UNITE-based self-amplifying RNA vaccine advances anti-tumor immunity in a murine triple-negative breast cancer model" on Friday, November 8th & Saturday, November 9th, 2024.

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Poster Presentation details are as follows:

Abstract: 223
Title: A UNITE-based self-amplifying RNA vaccine advances anti-tumor immunity in a murine triple-negative breast cancer model
Date and Time: Friday, November 8, 2024 ǀ 9:00 a.m.- 7:00 p.m. CST & Saturday, November 9, 2024 ǀ 9:00 a.m.- 8:30 p.m. CST
Poster Number: 223
Where: George R. Brown Convention Center, Level 1, Exhibit Halls AB
Speaker: Dr. Wei Shen, Ph.D.

About UNITE

ITI’s investigational UNITE platform, UNiversal Intracellular Targeted Expression, leverages the ability to engineer chimeric proteins, directing antigen presenting cells to present antigens to the immune system through a targeted pathway and driving a robust immune response. UNITE vaccines are distinct in that they combine two components: nucleic acid constructs that encode a specific antigen and an endogenous Lysosomal Associated Membrane Protein (LAMP-1) sequence. The UNITE platform harnesses LAMP-1 as a means of presenting the vaccine target to the immune system, resulting in antibody production, inflammatory cytokine release, and establishing critical immunological memory, something that other vaccine approaches commonly lack. This approach could put UNITE technology at the crossroads of immunotherapies in multiple indications, including cancer, human allergy, animal health, and infectious disease. Preclinical data is currently being developed to explore whether LAMP-1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and used to create immune responses in tumor types that otherwise do not provoke an immune response.