On October 4, 2022 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of injectable biologics designed to selectively engage and modulate tumor-specific T cells directly within the patient’s body, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to CUE-101, its lead clinical drug candidate from the CUE-100 series of interleukin 2 (IL-2)-based biologics, for the treatment of patients with human papilloma virus (HPV16+) recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) as a monotherapy and in combination with pembrolizumab (KEYTRUDA) (Press release, Cue Biopharma, OCT 4, 2022, View Source [SID1234621688]).

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"We are very pleased to have received Fast Track designation from the FDA for CUE-101. This designation not only underscores the large unmet need for patients with R/M head and neck cancer who currently rely on available non-targeted therapies, but also highlights the potential of CUE-101 to provide a significant clinical benefit," said Dr. Matteo Levisetti, senior vice president, Clinical Development of Cue Biopharma. "To date in its Phase 1b clinical trials, CUE-101 has demonstrated a favorable tolerability profile and single-agent anti-tumor activity in monotherapy as well as encouraging anti-tumor clinical activity in combination with pembrolizumab, supporting the potential to improve overall survival (OS) for these patients. We look forward to providing periodic updates and remain committed to advancing the development of CUE-101 to provide patients with a potentially more effective and better tolerated treatment option. We anticipate initiating a registrational trial for CUE-101 monotherapy by mid-2023."

Fast Track is a process designed to facilitate the development and expedite the review of drug candidates to treat serious conditions and fulfill an unmet medical need. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the therapeutic candidate’s development plan. Therapeutic candidates with Fast Track designation may be eligible for accelerated approval and priority review if supported by clinical data.

CUE-101 is currently being evaluated in a Phase 1b trial (NCT03978689) as a monotherapy for the treatment of second line and beyond patients with HPV16+ R/M HNSCC and as a first-line treatment in a Phase 1 dose escalation and expansion trial in combination with KEYTRUDA for the same patient population.

About HPV+ Recurrent or Metastatic Head and Neck Cancer
Human papilloma virus (HPV)-positive cancers account for more than 20,000 deaths each year in the U.S. and Europe. The majority of these cancers are driven by HPV16 which carries the E7 antigen targeted by CUE-101. Despite treatment with current standard of care, the majority of patients with metastatic disease will experience recurrence, significantly affecting quality of life and often leading to untimely death.

About CUE-101
CUE-101 is Cue Biopharma’s lead clinical drug candidate from the CUE-100 series of interleukin 2 (IL-2)-based biologics. It is designed to activate and expand HPV16 tumor-specific T cells by presenting two signals or "cues" to T cells. Signal #1 incorporates the HPV E7 protein, harbored by HPV-induced cancer cells, to provide selectivity through interaction with the HPV-specific T cell receptor. Signal #2 consists of an engineered IL-2 variant to stimulate the activity of T cells. To date, Cue Biopharma has established initial proof of concept with CUE-101 as a monotherapy and believes that the CUE-100 series has the potential to treat multiple cancer indications. CUE-101 is currently being evaluated for the treatment of HPV16+ driven R/M HNSCC as a monotherapy and in combination with pembrolizumab (KEYTRUDA).

On October 4, 2022 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immunogenic dysregulation that drive cancer, reported that it was awarded a Small Business Innovative Research (SBIR) grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) to conduct non-clinical studies to identify predictive and pharmacodynamic biomarkers of activity of ST101, a peptide antagonist of C/EBPβ, in patient-derived breast cancer models (Press release, Sapience Therapeutics, OCT 4, 2022, View Source [SID1234621687]).

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"We are grateful to have been awarded a Phase 2 SBIR grant from the NIH for ST101, which represents a continuation of our initial grant that supported the advancement of ST101 through Phase 1 clinical studies," said Jim Rotolo, Ph.D., VP, Translational Pharmacology and Head of Research of Sapience Therapeutics. "This grant allows us to further evaluate the efficacy of ST101 in patient-derived breast cancer models, which will inform patient selection criteria to enhance ST101’s ability to treat multiple types of difficult cancers."

Sapience CEO and President, Dr. Barry Kappel added, "With this funding, we aim to further showcase the therapeutic promise of disrupting C/EBPβ-driven oncogenic and immunosuppressive activity with ST101 in clinically relevant breast cancer models. We look forward to advancing ST101 through Phase 2 and towards patients in need."

This grant was supported by the National Cancer Institute of the National Institutes of Health under Award Number 2R44CA250786-02. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About ST101
ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). ST101-101 is an open-label, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: Phase 1 dose escalation/regimen exploration and Phase 2 dose expansion. In the ongoing Phase 2 dose expansion, Sapience is actively enrolling patients with GBM, metastatic cutaneous melanoma, castration-resistant prostate cancer and locally advanced or metastatic hormone-receptor positive breast cancer. In the ongoing dose escalation part of the study, ST101 has demonstrated clinical proof-of-concept with a durable RECIST 1.1-confirmed partial response (PR) in a patient with cutaneous melanoma and evidence of long-lasting stable disease in several additional patients. In the ongoing Phase 2 dose expansion part of the study, ST101 has demonstrated clinical proof-of-concept with a mRANO-confirmed partial response in a patient with recurrent GBM and evidence of long-lasting stable disease in several additional patients.

ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as orphan designations from the FDA for advanced melanoma, glioma and AML, and from the European Commission for the treatment of glioma.

On October 4, 2022 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported the appointment of Luke Walker, M.D., as Chief Medical Officer. Dr. Walker will lead the clinical development strategy and its execution for Harpoon Therapeutics and the product candidates derived from the company’s multiple technology platforms (Press release, Harpoon Therapeutics, OCT 4, 2022, View Source [SID1234621686]). Dr. Walker will report to Julie Eastland, Harpoon Therapeutics’ President and Chief Executive Officer, and his appointment was effective October 3, 2022.

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"I’m excited to join Harpoon Therapeutics and work alongside science-driven, collaborative colleagues, who are driven by the potential to impact patients’ lives by developing novel therapeutics," said Dr. Walker. "Harpoon has multiple ongoing clinical programs with product candidates which have demonstrated meaningful clinical activity to reach a broad set of patients with high unmet medical needs. I look forward to working with the Harpoon team to move these clinical-stage product candidates forward and to advance the company’s platforms in both hematologic and solid tumors."

Dr. Walker comes to Harpoon Therapeutics from Seagen Inc. where he most recently served as Vice President of Clinical Development and was responsible for overseeing the global development of multiple early-stage clinical programs. At Seagen, he previously served as Global Development Lead for TUKYSA (tucatinib) through its approval and market launch for HER2-positive metastatic breast cancer. Dr. Walker came to Seagen through the acquisition of Cascadian Therapeutics, after having led the clinical development of the tucatinib program there from its early stages, working closely with other members of the current Harpoon leadership team and Board of Directors to successfully advance its development into pivotal studies. He received his Medical Degree from the University of Oklahoma Health Sciences Center and completed fellowship training in Hematology and Medical Oncology at Oregon Health Sciences University. After training, he practiced several years as a clinical medical oncologist prior to his career in clinical drug development.

"Harpoon warmly welcomes Dr. Walker to our senior leadership team," said Julie Eastland, President and Chief Executive Officer of Harpoon Therapeutics. "His experience in leading clinical development, as well as interactions with key opinion leaders, investigators and investors provides a strong addition to the leadership group. Dr. Walker is a proven leader who has overseen the strategy for oncology therapeutics from early-stage programs through the successful completion of pivotal registrational trials and approvals, and we believe his addition will provide significant strength for our clinical programs, as we advance our lead T cell engager product candidates, HPN328 and HPN217, through the clinic."

Inducement Award under NASDAQ Listing Rule 5635(c)(4)

In connection with Dr. Walker’s appointment, Harpoon Therapeutics granted him an inducement non-qualified stock option to purchase an aggregate of 305,000 shares of Harpoon’s common stock.

The stock option grant has an exercise price per share equal to $1.08, Harpoon’s closing trading price on Nasdaq on the grant date, October 3, 2022, and will vest over four years, with 1/4 of the underlying shares vesting on the one-year anniversary of the grant date and 1/36th of the underlying shares vesting monthly thereafter over 36 months, subject to Dr. Walker’s continued service relationship with Harpoon through the applicable vesting dates.

The independent directors of Harpoon’s Board of Directors approved the award as an inducement material to Dr. Walker’s employment in accordance with Nasdaq Listing Rule 5635(c)(4).

On October 4, 2022 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported an update on its RAMP (Raf And Mek Program) clinical trials (Press release, Verastem, OCT 4, 2022, View Source [SID1234621685]).

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RAMP 201 in Patients with Recurrent Low Grade Serous Ovarian Cancer (LGSOC)

Verastem recently conducted a second planned interim analysis of the ongoing RAMP 201 trial among patients with recurrent LGSOC. Based on the results, including independently confirmed responses and no new safety signals, the Company is planning to meet with the U.S. Food and Drug Administration (FDA) in the fourth quarter to review the data set, discuss the go forward treatment regimen selection and align on a regulatory path forward.

"We are pleased with the encouraging results to date from our RAMP 201 trial in patients with recurrent low-grade serous ovarian cancer as we continue to see independently confirmed response rates, no new safety signals and a majority of patients still on treatment," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "As part of our Breakthrough Therapy Designation status and ongoing communications with the FDA, we look forward to our upcoming meeting to align on a regulatory path forward to advance this potential option for patients with LGSOC, who have a high unmet need and no approved therapies to treat their disease."

Since the first interim analysis announced in June, the trial has been continuing with all four cohorts (VS-6766 ± defactinib in KRAS mutant and KRAS wild type patient populations) with full enrollment based on the study protocol expected by the end of the year. Interim results will not be released at this time to ensure the integrity of this ongoing, registration-directed clinical trial.The Company will provide an update after the upcoming meeting with the FDA.

RAMP 202 in Patients with KRAS G12V-Mutant Non-Small Cell Lung Cancer

In a planned analysis of the Part A data from the RAMP 202 trial among patients with KRAS G12V NSCLC treated with the combination of VS-6766 and defactinib (n=19), the confirmed overall response rate (ORR) by independent review was 11% (2 of 19) with a disease control rate of 37%. The ORR with non-G12V KRAS mutations was 5% (2 of 37) (one confirmed and one unconfirmed by independent review) with a disease control rate of 54%, and no subtype was identified for further clinical evaluation of VS-6766 with defactinib in this trial. Verastem plans to present the Part A results of RAMP 202 at an upcoming medical congress.

"While this combination of VS-6766 and defactinib did not meet the pre-defined criteria to continue in the RAMP 202 trial, we remain optimistic about other combinations with VS-6766 in NSCLC," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "We will continue to analyze the results of the trial and include the findings in our development plans moving forward as we evaluate additional combinations for VS-6766 to best maximize its potential benefit."

RAMP 203 and RAMP 204 in Patients with KRAS G12C-Mutant NSCLC

The RAMP 203 Phase 1/2 trial to evaluate the safety, tolerability and efficacy of VS-6766 in combination with Amgen’s KRAS G12C inhibitor LUMAKRASTM (sotorasib) in patients with KRAS G12C-mutant NSCLC, has advanced to the Cohort 2 of 4mg VS-6766 in combination with 960mg of LUMAKRASTM. Initial results are expected by the fourth quarter of this year. The RAMP 204 Phase 1/2 trial of VS-6766 and Mirati’s adagrasib, which will determine the maximum tolerated dose and recommended Phase 2 dose for the combination and evaluate the safety, tolerability and efficacy of the combination in patients who have progressed on a KRAS G12C inhibitor, is open and enrolling.

These studies will investigate the potential benefits of a more complete vertical blockade of the RAS pathway as acquired resistance to KRAS G12C inhibitors in patients occurs predominantly through additional mutations in the RAS pathway, many of which could be addressed with a downstream inhibitor such as VS-6766.

RAMP 205 in Patients with Frontline Metastatic Pancreatic Cancer

The Company plans to open the RAMP 205 Phase 1b/2 clinical trial of VS-6766 with defactinib in addition to standard of care chemotherapy (gemcitabine/nab-paclitaxel regimen) in frontline metastatic pancreatic cancer in the fourth quarter of this year. The trial, in partnership with the Pancreatic Cancer Action Network (PanCAN) will evaluate whether a more complete blockade of KRAS signaling, which is mutated in more than 90% of pancreatic cancer tumors, will improve outcomes for patients with pancreatic cancer.

Corporate Updates

Intermittent dosing intellectual property for both VS-6766 alone (previously announced) and in combination with defactinib was recently allowed, extending patent coverage up to 2038 and 2040, respectively.

As of August 31, 2022, Verastem Oncology had cash, cash equivalents and investments of $110.4 million.

About VS-6766

VS-6766 is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. VS-6766 is currently in late-stage development.

In contrast to other MEK inhibitors, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp VS-6766, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp in RAS-driven tumors as part of its (Raf And Mek Program). RAMP 201 is a registration-directed trial of VS-6766 alone and in combination with defactinib in patients with recurrent LGSOC. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and adagrasib in combination with VS-6766 in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. As part of the "Therapeutic Accelerator Award" Verastem Oncology received from the Pancreatic Cancer Network (PanCAN), the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating VS-6766 and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

On October 4, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that it has entered into an agreement with Bristol Myers Squibb (NYSE: BMY) (Press release, Autolus, OCT 4, 2022, View Source [SID1234621684]). The agreement grants Bristol Myers Squibb access to incorporate Autolus’ proprietary RQR8 safety switch into an initial set of selected cell therapy programs on a target-by-target basis for the treatment of cancer, with an option for Bristol Myers Squibb to incorporate the RQR8 safety switch in additional cell therapy programs beyond the initial set of selected programs.

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Managing toxicities is a critical step in the successful application of programed cell therapies. Safety switches are designed to allow the use of pharmacological agents to selectively eliminate a cell therapy in the event a patient experiences severe adverse side effects from the treatment. Autolus’ proprietary RQR8 switch works by administration with the widely available and approved pharmaceutical antibody, rituximab. Once administered, rituximab binds to the engineered CD20 epitopes on the surface of the cell therapy and triggers selective cell death1.

Safety switches form part of Autolus’ industry-leading suite of cell programing modules that are designed to provide precise targeting, controlled, enhanced and sustained CAR T activity in a hostile tumor microenvironment.

Under the terms of the agreement, Autolus will receive an upfront payment for access to the RQR8 safety switch for the initial set of cell therapy programs with the potential for near term option exercise fees and development milestone payments. In addition, Autolus would be entitled to receive royalties on net sales of all Bristol Myers Squibb cell therapy products that incorporate the RQR8 safety switch.

"Safety switches are critical to the future of our field of advanced cell therapies. They allow us to develop approaches that are designed to significantly improve patient outcomes, whilst at the same time incorporating the potential to reduce the risk of severe adverse side effects from the treatment," said Dr. Martin Pule, CSO of Autolus. "Next-generation, modular CAR T innovation is at the core of Autolus and RQR8 is incorporated in several of our product candidates. We look forward to partnering with Bristol Myers Squibb to bring the potential utility of our proprietary safety switch to their programs. I would like to take this opportunity to thank our excellent research team at Autolus for their continued hard work."