On November 12, 2024 Servier reported that it will present data at the 29th Annual Meeting of the Society for Neuro-Oncology (SNO), November 21-24, 2024, in Houston, Texas (Press release, Servier, NOV 12, 2024, View Source [SID1234648224]). Data presentations will focus on the company’s neuro-oncology development program, including three oral-presentations, and reinforce our understanding of the burdens and experiences of people living with IDH-mutant glioma.

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"At Servier, we are dedicated to delivering transformative, life-changing therapies to patients living with cancer who have little-to-no options available," said Claude Bertrand, Executive Vice President Research and Development, Chief Scientific Officer, at Servier. "Our presentations at this year’s Society for Neuro-Oncology Conference reinforce our commitment to people living with IDH-mutant gliomas, who had, until recently, limited therapeutic options to treat this devastating disease. We look forward to sharing results with the community, including updated Phase 3 data that supports our recently approved medication for Grade 2 IDH-mutant gliomas."

A full list of company-sponsored abstracts can be found here.

About Glioma1

Gliomas are tumors that arise from glial or precursor cells within the central nervous system (CNS). The 2021 World Health Organization (WHO) classification recognizes four general groups of gliomas, one of which is adult-type diffuse gliomas. These diffuse gliomas are the most common primary malignant brain tumors in adults. The pathogenesis and prognosis of these tumors are tightly linked to mutations (or lack thereof) in the metabolic enzyme isocitrate dehydrogenase (IDH), and molecular testing is required for proper diagnosis. As of 2021, adult-type diffuse gliomas are sub-divided into only three categories:

Astrocytoma, IDH-mutant (CNS WHO grades 2-4)

Oligodendroglioma, IDH-mutant and 1p19q-codeleted (CNS WHO grades 2-3)

Glioblastoma, IDH-wildtype (CNS WHO grade 4)

On November 12, 2024 Astrazeneca reported positive high-level results of KOMET, the largest, global randomised double-blind placebo-controlled multicentre Phase III trial in adults with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN), showed that Koselugo (selumetinib), an oral, selective MEK inhibitor, met its primary endpoint, demonstrating a statistically significant and clinically meaningful objective response rate (ORR) versus placebo in these adult patients (Press release, AstraZeneca, NOV 12, 2024, View Source [SID1234648223]).

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NF1 is a rare, progressive genetic condition affecting an estimated 1.7 million individuals worldwide, approximately 70% of whom are adults.1,2 In 30-50% of patients, tumours develop on the nerve sheaths and may cause debilitating symptoms.3-8 NF1 is usually diagnosed in early childhood, however, NF1 often progresses into adulthood.9,10 There are no approved treatments for adults, leaving many to experience disfigurement, dysfunction, persistent pain or endure multiple surgeries.11

Prof. Ignacio Blanco Guillermo, MD, PhD, Chairman of the Genetic Counselling and Clinical Genetics Programme at the Germans Trias i Pujol University Hospital, Chairman of the Spanish National Reference Centre for Adult Patients with Neurofibromatosis and Principal Investigator of the KOMET trial, said: "With limited options to manage NF1 PN in adults, many patients experience functional impairment and symptoms, which can substantially impact their lives. These clinically meaningful data show Koselugo has the potential to make a positive impact in patient care by reducing the size of plexiform neurofibromas."

Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: "These promising results demonstrate that Koselugo, the first and only approved targeted therapy for certain children with NF1 PN, now has the potential to benefit adult patients for whom there are no approved targeted therapies. As the largest and only global placebo-controlled Phase III trial in adults with NF1 PN, KOMET reinforces our leadership in advancing potential treatment options for people living with this debilitating disease. We look forward to sharing these findings with regulatory authorities."

Scot Ebbinghaus, MD, Vice President, Global Clinical Development, MSD Research Laboratories, said: "Adults with NF1 are in critical need of treatment options to help manage symptomatic, inoperable plexiform neurofibromas. These positive results from the Phase III KOMET trial demonstrate the potential to expand the use of Koselugo beyond paediatric patients to also treat adult patients living with this rare and challenging genetic condition."

In the trial, ORR was defined as the percentage of patients with confirmed complete response (disappearance of PNs) or partial response (at least 20% reduction in tumour volume) by cycle 16 (28 days per cycle) as determined by independent central review (ICR) per response evaluation in neurofibromatosis and schwannomatosis (REiNS) criteria.

The safety profile of Koselugo in this study was consistent with that observed in clinical trials among children and adolescents. No new safety signals were identified.

Alexion, AstraZeneca Rare Disease will share these data with regulatory authorities and present at a forthcoming medical meeting. AstraZeneca and MSD are jointly developing and commercialising Koselugo globally.

Notes

NF1
NF1 is a rare, progressive, genetic condition that is caused by a spontaneous or inherited mutation in the NF1 gene.3,11 NF1 is associated with a variety of symptoms, including soft lumps on and under the skin (cutaneous neurofibromas) and, in 30-50% of patients, tumours develop on the nerve sheaths (PNs).4,11 These PNs can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment and bladder or bowel dysfunction.4-8 PNs begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.5,8,11,12

KOMET
KOMET is a global Phase III randomised, double-blind, placebo-controlled, multicentre trial designed to evaluate the efficacy and safety of Koselugo in adults with NF1 who have symptomatic, inoperable PNs. The trial enrolled 145 adults from 13 countries across North America, South America, Europe, Asia and Australia, with participants’ baseline characteristics, including gender and distribution of PNs, reflective of the global adult NF1 patient population. Patients were enrolled and randomised to receive Koselugo or placebo (1:1) for 12 28-day cycles. Participants were required to have diagnosis of NF1, at least one symptomatic, inoperable PN measurable by volumetric MRI analysis, chronic PN pain score documented during screening, adequate organ and marrow function and stable chronic PN pain medication use at enrolment.13

The primary endpoint is confirmed ORR by cycle 16 as assessed by ICR. ORR is defined as the percentage of patients with confirmed complete response (disappearance of PNs) or partial response (at least 20% reduction in tumour volume).13

After 12 cycles, patients on placebo were switched to Koselugo and patients on Koselugo remained on treatment for an additional 12 cycles. Patients who had the opportunity to complete 24 cycles of treatment have the option to participate in a long-term extension period and continue to receive Koselugo.13

Koselugo
Koselugo (selumetinib) is a kinase inhibitor that blocks specific enzymes (MEK1 and MEK2), which are involved in stimulating cells to grow. In NF1, these enzymes are overactive, causing tumour cells to grow in an unregulated way creating so-called plexiform neurofibromas (PN). By blocking these enzymes, Koselugo slows down the growth of tumour cells and, therefore, the PN growth.

Koselugo is approved in the US, EU, Japan, China and other countries and has been granted Orphan Drug Designation in the US, EU, Japan and other countries for the treatment of certain paediatric patients with NF1 who have symptomatic, inoperable PN.

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.