On November 12, 2024 AstraZeneca and Daiichi Sankyo reported to have submitted a new Biologics License Application (BLA) for accelerated approval in the US for datopotamab deruxtecan (Dato-DXd) for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFR) non-small cell lung cancer (NSCLC) who have received prior systemic therapies, including an EGFR-directed therapy (Press release, AstraZeneca, NOV 12, 2024, View Source [SID1234648222]).

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The companies have voluntarily withdrawn the BLA in the US for datopotamab deruxtecan for patients with advanced or metastatic nonsquamous NSCLC based on the TROPION-Lung01 Phase III trial.

The decision to submit a new BLA for EGFR-mutated NSCLC and withdraw the previously submitted BLA for nonsquamous NSCLC was informed by feedback from the US Food and Drug Administration (FDA).

The new BLA is based on results from the TROPION-Lung05 Phase II trial and supported by data from the TROPION-Lung01 Phase III and TROPION-PanTumor01 Phase I trials. New results from a pooled analysis of patients with previously treated EGFR-mutated NSCLC in the TROPION-Lung05 and TROPION-Lung01 trials will be featured in a late-breaking presentation at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia 2024 Congress (LBA7).

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "TROPION-Lung01 was designed to test the potential to improve upon standard-of-care chemotherapy in a broad, previously treated, advanced lung cancer patient population. The results, together with data from TROPION-Lung05, showed an especially pronounced benefit for patients with an EGFR mutation which informed our discussions with the FDA and the decision to seek accelerated approval of datopotamab deruxtecan in this patient population. TROPION-Lung01 has also provided exciting exploratory data supporting our biomarker development, which will be validated in ongoing and planned Phase III lung cancer trials."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "Treating EGFR-mutated non-small cell lung cancer is incredibly challenging following disease progression given that the complexity and variability of these mutations often lead to resistance. The potential approval of datopotamab deruxtecan could offer renewed hope for patients with this formidable disease."

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and with Tagrisso (osimertinib) as treatment for patients with advanced or metastatic EGFR-mutated nonsquamous NSCLC in the ongoing TROPION-Lung14 and TROPION-Lung15 Phase III trials. In addition, ongoing Phase III trials in 1st-line advanced or metastatic nonsquamous NSCLC, AVANZAR and TROPION-Lung10, have the potential to validate the QCS (quantitative continuous scoring) biomarker for TROP2 identified in an exploratory analysis of TROPION-Lung01. An additional trial in patients with biomarker-positive tumours in the 2nd-line nonsquamous NSCLC setting is also planned.

Notes

Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 Lung cancer is broadly split into small-cell lung cancer (SCLC) or NSCLC, the latter accounting for about 80% of cases.2 Approximately 10-15% of patients with NSCLC in the US and Europe, and 30-40% of patients in Asia have an EGFR mutation.3,4 The majority of EGFR mutations occur in tumours of nonsquamous histology.5

For patients with tumours that have an EGFR mutation, the established 1st-line treatment in the metastatic setting is an EGFR-tyrosine kinase inhibitor (TKI).6 While EGFR-TKIs have improved outcomes in the 1st-line setting, most patients eventually experience disease progression and receive chemotherapy.7-10

TROP2 is a protein broadly expressed in the majority of NSCLC tumours.11 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.6,12

TROPION-Lung05
TROPION-Lung05 is a global, multicentre, single-arm, open-label Phase II trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on or after one regimen of platinum-based chemotherapy and at least one TKI (with or without other systemic therapies). Patients receiving up to four prior lines of treatment with tumours with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial.

The primary trial endpoint of TROPION-Lung05 is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary efficacy endpoints include duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS) and safety.

TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America. For more information visit ClinicalTrials.gov.

TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DOR, TTR, and DCR as assessed by both BICR and investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

Primary PFS and interim OS results from TROPION-Lung01 were presented at the ESMO (Free ESMO Whitepaper) 2023 Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer and simultaneously published in the Journal of Clinical Oncology in September 2024.

TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with NSCLC to assess the safety and tolerability of datopotamab deruxtecan to determine the recommended dose for expansion (6 mg/kg). The dose expansion part of TROPION-PanTumor01 is enrolling several different cohorts including patients with NSCLC, triple-negative breast cancer (TNBC), HR-positive, HER2-low or negative breast cancer, SCLC, urothelial, gastric, pancreatic, castration-resistant prostate and esophageal cancer.

Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, TTR, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.

TROPION-PanTumor01 enrolled approximately 900 patients in Asia and North America. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, TNBC and HR-positive, HER2-low or negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.

On November 12, 2024 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported financial results for the third quarter of 2024 and provided an overview of its clinical programs and anticipated milestones (Press release, Vincerx Pharma, NOV 12, 2024, View Source [SID1234648221]).

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"As we direct our efforts and resources toward our ADC technologies and programs, we are committed to advancing VIP943 based on the encouraging safety, efficacy, and tolerability results observed to date. We look forward to presenting additional data from patients at efficacious dose cohorts by early next year," said Ahmed Hamdy, M.D., Chief Executive Officer. "Securing the funding necessary to advance our programs remains a priority. Alongside exploring financing options, we remain focused on strategic partnerships, particularly as pharmaceutical companies intensify their search for truly differentiated and transformative technologies."

THIRD QUARTER 2024 CLINICAL PROGRAM HIGHLIGHTS AND ANTICIPATED MILESTONES

VIP943

VIP943 is a novel CD123-targeted ADC developed with the Company’s next-generation VersAptx platform.
VIP943 has shown promising safety, efficacy, and tolerability in an ongoing Phase 1 dose-escalation study for patients with relapsed/refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and B-cell acute lymphoblastic leukemia (B-ALL) (NCT06034275). In October, the Company reported two complete responses in this Phase 1 study: one out of four patients with relapsed AML in the 1 mg/kg dose cohort achieved complete remission with incomplete hematologic recovery (CRi), and one out of one patient with higher-risk MDS in the 1.3 mg/kg dose cohort achieved complete remission with limited count recovery (CRL).
VIP943 has shown effective target engagement and elimination of CD123+ malignant cells, with pharmacodynamic data demonstrating decreases in CD123+ blasts after dosing. Preliminary pharmacokinetic data indicates minimal payload release (≤1% in plasma), signifying a stable linker.
Given the favorable safety and tolerability observed for VIP943, the Company continues dose escalation to assess potential for additional efficacy. Enrollment in the once-weekly and twice-weekly (as an induction therapy) dosing schedules is ongoing.
Vincerx expects to share additional Phase 1 study data for VIP943 by early 2025.
Enitociclib

Enitociclib is a highly selective CDK9 inhibitor designed to block the activation of RNA polymerase II, leading to inhibition of oncogenes, including MYC and MCL1.
Enitociclib is currently in a Phase 1 dose-escalation study (NTC05371054) evaluating the combination of enitociclib, venetoclax, and prednisone in diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). This study is being conducted in collaboration with the National Institutes of Health (NIH). As of September 2024, the study reported four partial responses (PRs) in seven patients (57% overall response rate), including one patient with double hit lymphoma (DH-DLBCL) and three patients with PTCL.
Enitociclib has successfully completed its Phase 1 dose-escalation study as a monotherapy (NCT02635672), enrolling 63 patients across dose-escalation and expansion cohorts. The treatment demonstrated a favorable safety profile, dose-proportional pharmacokinetics, and on-target pharmacodynamic activity. Clinical benefits included durable complete metabolic remissions in two patients with DH-DLBCL, lasting 3.7 and 2.3 years, with both remissions continuing more than two years after treatment cessation. In addition, a transformed follicular (tFL) patient achieved a PR with a 63% tumor reduction after nearly two years, a meaningful outcome given the historically poor prognosis of tFL. Furthermore, 13 patients with solid tumors achieved stable disease as their best response, including five ovarian cancer patients—indicating a promising path for future combination studies in this indication.
The Company is actively focused on finding a strategic partner to continue the development of this asset.
VIP236

VIP236 is a αVβ3 SMDC conjugated to an optimized camptothecin (CPT) payload developed with the Company’s VersAptx platform.
VIP236 has completed its Phase 1 dose-escalation study (NCT05712889), identifying the maximum tolerated dose that could be utilized in future studies. As reported in October, a total of 29 patients were enrolled in the Phase 1 study, resulting in a 45% disease control rate. The drug demonstrated a favorable safety profile, distinguishing itself from other CPTs by showing no instances of common dose-limiting side effects such as life-threatening diarrhea, severe stomatitis/mucositis, or interstitial lung disease.
The Company intends to identify a partner to champion VIP236 through further development.

THIRD QUARTER 2024 FINANCIAL RESULTS

Vincerx had approximately $10.1 million in cash, cash equivalents, and marketable securities as of September 30, 2024, as compared to approximately $16.3 million as of June 30, 2024. Based on its current business plans and assumptions, Vincerx believes its available capital will be sufficient to meet its operating requirements into early 2025.
Research and development expenses for the third quarter ended September 30, 2024, were approximately $3.9 million, as compared to approximately $6.1 million for the same period in 2023. This decrease is primarily the result of decreases in research services of approximately $2.4 million and personnel-related expenses of approximately $0.8 million, offset by an increase in clinical-related expenses of approximately $0.9 million.
General and administrative expenses for the third quarter ended September 30, 2024, were approximately $3.9 million, as compared to approximately $3.5 million for the same period in 2023. This increase was due to a $0.5 million increase in professional services, partially offset by a decrease in personnel-related expenses of $0.1 million.
For the third quarter ended September 30, 2024, Vincerx reported a net loss of approximately $7.8 million, or $0.17 per share. For the third quarter ended September 30, 2023, Vincerx reported a net loss of approximately $9.0 million, or $0.42 per share.

On November 12, 2024 Turnstone Biologics Corp. ("Turnstone" or the "Company") (Nasdaq: TSBX), a clinical-stage biotechnology company developing a differentiated approach to treat and cure patients with solid tumors by pioneering selected tumor-infiltrating lymphocyte (Selected TIL) therapy, reported financial results for the third quarter ended September 30, 2024, and provided recent business highlights (Press release, Turnstone Biologics, NOV 12, 2024, View Source [SID1234648220]).

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"Earlier this quarter, we announced a corporate restructuring and the decision to focus resources on our Phase 1 program, TIDAL-01, which we believe puts us on the path to significant value creation. Importantly, our extended cash runway into the second quarter of 2026 enables us to achieve potential key clinical milestones and we remain steadfast in advancing our differentiated approach to TIL therapy for cancer patients with high unmet need," said Sammy Farah, M.B.A., Ph.D., Turnstone’s President and Chief Executive Officer. "Recently, we reported initial clinical data from our STARLING trial which showcased durable anti-tumor activity in a heavily pre-treated late-line microsatellite stable colorectal cancer patient population, including the achievement of a complete response. The patient remains in remission with progression-free survival extending beyond one year. Our encouraging initial clinical data, combined with results that continue to emerge from within the field in support of selection-based approaches, strengthen the competitive profile of our next-generation selected TIL technology and its potential to treat solid tumors. We look forward to sharing our next clinical update in 1H 2025."

Third Quarter 2024 and Recent Business Highlights

Presented at the 2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting – Tumor Infiltrating Lymphocytes (TIL) Symposium, supporting ongoing clinical efforts. On November 6, 2024, Turnstone delivered a presentation titled "TIDAL-01: Enriching for a More Potent TIL Population with Selected TIL therapy" at the SITC (Free SITC Whitepaper) TIL Symposium in Houston, TX. The presentation showcased Turnstone’s initial clinical data from its Phase 1 TIDAL-01 program, including the achievement of a complete response in a third-line microsatellite stable metastatic colorectal cancer ("MSS mCRC") patient. Additionally, two posters were presented at the SITC (Free SITC Whitepaper) Annual Meeting with preclinical data that demonstrated the practicality of selecting and expanding tumor-reactive TIL as a potential treatment option for patients with solid tumors.

Reported positive initial data from the STARLING Phase 1 Trial of TIDAL-01 in MSS mCRC. In August, initial results were shared from the first 4 evaluable MSS mCRC patients from the STARLING Phase 1 study of TIDAL-01. The trial yielded a 25% overall response rate ("ORR") with durable clinical benefit and 50% disease control rate ("DCR") in a heavily pre-treated, advanced disease, third-line setting where patients are unresponsive to checkpoint inhibitors and have almost no treatment options. One patient had a complete response ("CR") and has been progression-free for over one year which is notable in this patient population, while another patient had stable disease ("SD") for 6 months. As a point of comparison, the current standard of care treatment for this patient population has resulted in an ORR of 1-6% and a median progression-free survival ("mPFS") of 2-5.6 months. There were also no new safety observations specific to Turnstone’s Selected TILs.

Completed strategic restructuring and portfolio review to extend cash runway. In October, Turnstone announced the streamlining of its operations to optimize its portfolio and strengthen its financial position to focus on achieving clinical milestones. Key initiatives include:

•
Pipeline strategy and prioritization: Following a comprehensive evaluation of the business, Turnstone has decided to sharpen its focus on development of the TIDAL-01 program.
•
Organizational restructuring: The Company executed a 60% workforce reduction to prioritize the development of its core Selected TIL program and extend its cash runway.

•
Financial strategy: Turnstone expects its cash runway to support operations and clinical development through the second quarter of 2026.
•
Talent strategy: As part of Turnstone’s updated corporate strategy, Ines Verdon, M.D., Senior Vice President of Clinical Development, is assuming leadership of all clinical activities. Michael Fitch, Ph.D., has been promoted to Senior Vice President of Manufacturing and will oversee all manufacturing and technical operations activities. Wendy Worcester, CPA, is assuming the responsibility of the Finance function as the Principal Financial and Accounting Officer. Saryah Azmat has been promoted to Chief Operating Officer.

Third Quarter 2024 Financial Results

Cash, cash equivalents and short-term investments: As of September 30, 2024, cash, cash equivalents and short-term investments were $45.3 million. The Company expects that the combined cash, cash equivalents and short-term investments will be sufficient to fund its operations into the second quarter of 2026.

Research and development (R&D) expenses: R&D expenses for the three months ended September 30, 2024, were $14.4 million, compared to $14.2 million for the same period in 2023. The increase was due primarily to an increase in manufacturing, clinical, and regulatory costs related to TIDAL-01 clinical trials.

General and administrative (G&A) expenses: G&A expenses for the three months ended September 30, 2024, were $3.9 million, compared to $4.8 million for the same period in 2023. The decrease was due primarily to reductions in personnel costs, professional service costs, and other general and administrative costs.

Net loss: Net loss for the three months ended September 30, 2024, was $17.0 million, compared to net loss of $17.3 million for the same period in 2023.

On November 12, 2024 TScan Therapeutics, Inc. (Nasdaq: TCRX), a clinical-stage biotechnology company focused on the development of T cell receptor (TCR)-engineered T cell (TCR-T) therapies for the treatment of patients with cancer, reported financial results for the third quarter ended September 30, 2024, and provided a corporate update (Press release, TScan Therapeutics, NOV 12, 2024, View Source [SID1234648219]).

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"As we approach the end of the year, we remain committed to advancing our clinical-stage pipeline across both heme and solid tumor malignancies and providing an update on the ALLOHA Phase 1 trial following ASH (Free ASH Whitepaper). We are encouraged to see that none of the 16 patients on the treatment arm relapsed, including five patients at least one-year post-transplant as of the July 8th abstract cutoff date. We look forward to sharing updated data, including several additional patients, at ASH (Free ASH Whitepaper)," said Gavin MacBeath, Ph.D., Chief Executive Officer. "During the third quarter we continued to prioritize screening, enrolling, and dosing patients in the solid tumor program and remain on track to dose our first patient with multiplex therapy and provide an update on our Phase 1 study by the end of the year."

Recent Corporate Highlights

•
The Company recently announced an upcoming oral presentation at the 66th ASH (Free ASH Whitepaper) Annual Meeting. The data in the abstract included 16 treatment-arm patients and 11 control-arm patients with a data cutoff of July 8, 2024. No dose limiting toxicities were observed across all treatment-arm patients and the safety profile was generally consistent with hematopoietic cell transplantation (HCT). All treatment-arm patients (16 of 16) were relapse-free and minimal residual disease (MRD)-negative as of the data cutoff, whereas three control-arm patients (3 of 11) relapsed, two of whom died from their disease. These data support both the safety and potential of TSC-100 and TSC-101 to reduce relapses and increase relapse-free survival in patients receiving reduced intensity conditioning HCT. Updated data will be presented at the annual meeting.

•
The Company will host a virtual KOL event featuring Ran Reshef, M.D., M.Sc., on Tuesday, December 10th, at 8:00 a.m. ET to discuss the data presented at the ASH (Free ASH Whitepaper) Annual Meeting. The Company will also discuss its clinical development strategy for the heme program. Dr. Reshef is the Professor of Medicine and Director of the Cellular Immunotherapy Program at Columbia University Irving Medical Center. Additional details around the call will be provided closer to the event. Registration for the event can be found here.

•
The Company recently increased its internal manufacturing capacity as well as identified a global contract development and manufacturing organization (CDMO) with commercial capabilities to support both the heme
and solid tumor programs. The Company is on track to transfer the commercial heme manufacturing process to the CDMO in 2025.

•
The Company recently presented three posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting held in Houston, TX and virtually:

o
Discovery of a MAGE-A4-specific TCR-T Therapy Candidate for Multiplex Treatment of Solid Tumors
o
Preclinical Models for T-Plex, a Customized Multiplexed TCR-T Cell Therapy Addressing Intra-Tumor Antigen and HLA Heterogeneity
o
Development of a Target Agnostic Platform to Assess the Reactivity of T Cell Receptor (TCR)-Engineered T Cell (TCR-T) Therapies to Primary Human Tissues

Copies of the presentation materials can be found under the "Publications" section of the Company’s website at tscan.com.

Upcoming Anticipated Milestones

Heme Malignancies Program: TScan’s two lead TCR-T therapy candidates, TSC-100 and TSC-101, are designed to treat residual disease and prevent relapse in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) undergoing allogeneic HCT (the ALLOHATM trial, NCT05473910).

G&A Expenses: General and administrative expenses for the third quarter of 2024 were $7.4 million, compared to $5.9 million for the third quarter of 2023. The increase of $1.5 million was primarily driven by an increase in personnel expenses due to increased headcount to support business activities. General and administrative expenses included non-cash stock compensation expense of $1.3 million and $0.4 million for the third quarter of 2024 and 2023, respectively.

Net Loss: Net loss was $29.9 million for the third quarter of 2024, compared to $23.0 million for the third quarter of 2023, and included net interest income of $2.7 million and $1.8 million, respectively.

Cash Position: Cash, cash equivalents, and marketable securities as of September 30, 2024, were $271.1 million, excluding $5.0 million of restricted cash. The Company believes that its existing cash resources will continue to fund its current operating plan into the fourth quarter of 2026.

Share Count: As of September 30, 2024, the Company had issued and outstanding shares of 53,354,124, which consists of 49,077,536 shares of voting common stock and 4,276,588 shares of non-voting common stock, and outstanding pre-funded warrants to purchase 65,587,945 shares of voting common stock at an exercise price of $0.0001 per share.

•
Plans to open expansion cohorts at the proposed recommended Phase 2 dose level to further characterize safety and evaluate translational and efficacy endpoints by the end of 2024.
•
One-year clinical and translational data on initial patients to be reported by the end of 2024.
•
Initiate a registration trial, pending feedback from regulatory authorities, and plans to report two-year clinical and translational data in 2025.

Solid Tumor Program: TScan continues to expand the ImmunoBank, a collection of therapeutic TCR-Ts that target different cancer-associated antigens presented on diverse HLA types. TScan’s strategy is to treat patients with multiple TCR-Ts to overcome tumor heterogeneity and prevent resistance that may arise from either target or HLA loss (screening protocol: NCT05812027; treatment protocol: NCT05973487).

•
Actively screening, enrolling, and dosing patients across the TCR-T therapy candidates.
•
Update on solid tumor program expected by the end of 2024.
•
Investigational new drug (IND) filing for TCR targeting MAGE-A4 on HLA-A*02:01 (TSC-202-A0201) planned by the end of the year.
•
Response data for multiplex therapy anticipated in 2025.

Third Quarter 2024 Financial Results

Revenue: Revenue for the third quarter of 2024 was $1.0 million, compared to $3.9 million for the third quarter of 2023. The decrease was primarily due to timing of research activities pursuant to the Company’s collaboration agreement with Amgen which commenced in May 2023.

R&D Expenses: Research and development expenses for the third quarter of 2024 were $26.3 million, compared to $22.7 million for the third quarter of 2023. The increase of $3.5 million was primarily driven by an increase in clinical studies expense associated with the ongoing enrollment of our ALLOHA Phase 1 heme trial and start-up activities and initial enrollment in our Phase 1 solid tumor clinical trial, as well as an increase in personnel expenses due to additional headcount in support of our expanded research and development activities. Research and development expenses included non-cash stock compensation expense of $1.2 million and $0.9 million for the third quarter of 2024 and 2023, respectively.

On November 12, 2024 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity, reported financial results for the third quarter ended September 30, 2024, and provided corporate updates (Press release, Terns Pharmaceuticals, NOV 12, 2024, View Source [SID1234648218]).

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"Our progress in the third quarter was highlighted by the compelling topline results from our Phase 1 study of TERN-601, which demonstrated class-leading potential as a differentiated, once-daily, oral GLP-1R agonist for the treatment of obesity and supports its rapid advancement into Phase 2 studies," stated Amy Burroughs, chief executive officer of Terns. "We are looking forward to sharing interim dose escalation data from the Phase 1 CARDINAL trial of TERN-701 as a treatment for chronic myeloid leukemia (CML) and expect this early look at safety, tolerability and signals of efficacy to reinforce its potential as a best-in-class allosteric for the treatment of CML. Importantly, our successful equity raise underscores the strong support for our promising pipeline of differentiated small molecules, funds Terns through multiple catalysts across our clinical development programs and extends our cash runway into 2028."

Recent Pipeline Developments and Anticipated Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia (CML)

•
Interim data from initial dose escalation cohorts in Terns’ ongoing Phase 1 CARDINAL study of TERN-701 in CML expected in early December 2024
o
CARDINAL is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, pharmacokinetics (PK) and efficacy of TERN-701 in patients with previously treated CML
o
The Company expects to share interim dose escalation data from the CARDINAL study, including safety, tolerability and early signals of efficacy
•
In August, Terns hosted a TERN-701 webinar event focused on interpreting early datasets in CML

TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

•
Terns plans to initiate a Phase 2 clinical trial in early second quarter of 2025 with initial 12-week data expected in the second half of 2025
o
The trial will begin with a 12-week portion to optimize dose titration and inform subsequent cohorts
•
In September, Terns announced positive safety and 28-day weight loss data from the Phase 1 first-in-human clinical trial of TERN-601 in obese and overweight participants
o
The results showed TERN-601 was well tolerated and demonstrated dose-dependent, statistically significant mean weight loss up to 5.5% (4.9% placebo adjusted) over 28 days
o
67% of study participants lost 5% or more of their baseline body weight at the highest dose of 740 mg once-daily (QD)
o
TERN-601 exhibited distinct properties for an oral GLP-1R agonist

▪
Low solubility and high gut permeability allowed for prolonged absorption and sustained target coverage and a flat PK curve, while high drug levels in the gut wall may lead to robust GLP-1R activation in the gut triggering satiety centers in the brain
▪
Low free fraction in circulation, combined with the flat PK curve, may contribute to TERN-601’s tolerability profile at higher target doses than other oral GLP-1R agonists
o
TERN-601 was well-tolerated with no treatment-related dose interruptions, reductions, or discontinuations even with rapid dose titration
TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist

•
In June, Terns presented new preclinical data at the American Diabetes Association (ADA) 84th Scientific Sessions supporting TERN-501 in combination with a GLP-1 receptor agonist for obesity
o
Preclinical findings demonstrated TERN-501 in combination with semaglutide significantly enhanced weight loss and showed proportionally greater loss of fat mass relative to lean mass compared to semaglutide alone
o
Supports the potential for TERN-501 as a combination partner for injectable and oral GLP-1 agonists for use in obesity and other metabolic disorders
o
The full poster is available on Terns’ scientific publications website
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Terns continues to evaluate opportunities for TERN-501 in metabolic diseases
TERN-800 Series: Oral, small-molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist

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Discovery efforts are ongoing for small molecule GIPR modulators for obesity, which have the potential for combination with GLP-1 receptor agonists, such as TERN-601
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Terns is prioritizing its discovery efforts on nominating a GIPR antagonist development candidate based on in-house discoveries and growing scientific rationale supporting the potential of GLP-1 agonist/GIPR antagonist combinations for obesity
Corporate Updates

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In September, Terns completed an upsized public offering of 14,064,048 shares of its common stock and 2,380,952 pre-funded warrants, generating gross proceeds of approximately $172.7 million before deducting underwriting discounts and commissions and other offering expenses, which extends the Company’s cash runway into 2028
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In July, Terns appointed Elona Kogan as Chief Legal Officer

Third Quarter 2024 Financial Results

Cash Position: As of September 30, 2024, cash, cash equivalents and marketable securities were $372.8 million, as compared with $263.4 million as of December 31, 2023. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2028.

Research and Development (R&D) Expenses: R&D expenses were $15.2 million for the quarter ended September 30, 2024, as compared with $14.8 million for the quarter ended September 30, 2023.

General and Administrative (G&A) Expenses: G&A expenses were $9.8 million for the quarter ended September 30, 2024, as compared with $18.4 million for the quarter ended September 30, 2023.

Net Loss: Net loss was $21.9 million for the quarter ended September 30, 2024, as compared with $29.8 million for the quarter ended September 30, 2023.