On June 4, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the presentation of new data from the ongoing Phase 1 studies of SRF388 and SRF617 (Press release, Surface Oncology, JUN 4, 2021, View Source [SID1234583560]). Data from the SRF388 study are to be presented in a scientific poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, being held virtually June 4-8, 2021 . In conjunction, Surface will host a webcast on Friday, June 4, 2021, at 8:00 a.m. ET to provide updates on both SRF388 and SRF617.

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"Generating evidence of monotherapy activity is a highly sought after, yet elusive, goal in immuno-oncology and we are excited to report that one of our molecules, SRF388, has produced a partial response in a heavily pretreated patient with lung cancer," said Rob Ross, M.D., chief executive officer. "These findings validate our scientific rationale and represent an important step forward in our pursuit of transformative treatments to help patients with cancer. We are also pleased to report that SRF617 continues to demonstrate good tolerability with evidence of biological activity. Moving forward, we are opening monotherapy and combination cohorts for both molecules across a range of tumor types, informed by the data we have generated to date."

"SRF388 is an antibody against IL-27, an immunosuppressive cytokine that plays a key role in controlling immunotolerance to cancer. These data from the ongoing SRF388 Phase 1 clinical study reinforce the potential benefit of IL-27 blockade as a promising anticancer strategy, particularly given the monotherapy partial response in a patient with PD-1-refractory lung cancer," said Amita Patnaik, M.D., co-director of clinical research at the START Center for Cancer Care in San Antonio, Texas, and lead author of the SRF388 results summary presented at ASCO (Free ASCO Whitepaper).

SRF388 Highlights:

Preliminary SRF388 results indicate promising single-agent activity in a heavily pretreated population, including a confirmed partial response demonstrating 66% tumor shrinkage and symptomatic improvement in a patient with squamous cell non-small-cell lung carcinoma (NSCLC), whose disease was resistant to three prior regimens including chemotherapy and PD-1 blockade.

In addition, there was evidence of disease stabilization, with 6 of 18 (33%) of evaluable patients experiencing disease stabilization at eight weeks and five (28%) persisting beyond 16 weeks.
SRF388 was well tolerated at all doses tested, with no dose-limiting toxicity observed to date, and with only low-grade treatment-related adverse events.
The recommended Phase 2 dose of 10 mg/kg was confirmed based on observed efficacy, tolerability, optimal pSTAT1 inhibition and pharmacokinetics.
SRF617 Highlights:

Early data from combination cohorts point to SRF617’s potential as a combination therapy, including an unconfirmed partial response with an approximately 50% tumor shrinkage in a patient with pancreatic cancer receiving second-line treatment with SRF617 in combination with gemcitabine/albumin-bound paclitaxel (Abraxane).

In addition, with SRF617 monotherapy, 7 of 19 evaluable patients (37%) achieved disease stabilization at eight weeks, with 4 (21%) persisting beyond 16 weeks.
SRF617 was well tolerated at all tested doses as a monotherapy and has a tolerability profile that is conducive to combination strategies.
"Results from both ongoing clinical trials support further evaluation of SRF388 and SRF617 as monotherapies and in combination with standard and investigational regimens in both immune checkpoint naïve and experienced patients," said Alison O’Neill, M.D., chief medical officer. "We’re pleased to see a profile allowing patients in both studies to escalate to higher doses with good tolerability."

Presentation at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper):

Presentation Type: e-poster (Abstract: 2551)
Title: Results of a phase 1 study of SRF388, a first-in-human, first-in-class, high-affinity anti-IL-27 antibody in advanced solid tumors
Session: Developmental Therapeutics – Immunotherapy
Lead Authors: Amita Patnaik, M.D. and Daniel Morgensztern, M.D.

The ASCO (Free ASCO Whitepaper) e-poster website will be launched on Friday, June 4, 2021, and will remain available for viewing through Tuesday, July 6, 2021. The full poster can be found on Surface Oncology’s website following the presentation.

Webcast Information:

The webcast, scheduled for June 4, 2021, at 8:00 a.m. ET, can be accessed online, and by telephone by dialing (866) 394-2883 (US/Canada) or (314) 888-4236 (international) five minutes prior to the start time and referring to conference ID 4567647. A recording of the webcast will be posted on the Surface website and available on-demand for one year.

About the SRF388-101 Clinical Trial:
The trial is a Phase 1, open-label, multicenter, first-in-human dose-escalation trial of SRF388, a monoclonal antibody targeting IL-27, conducted in patients with advanced solid tumors refractory to standard therapy. The first portion of the study will establish the preliminary safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SRF388 as a monotherapy and identify a dose suitable for expansion studies. In the second portion of the study, indication-specific expansion cohorts will evaluate the safety, preliminary efficacy, tolerability, PK and PD of SRF388 monotherapy and SRF388 in combination with pembrolizumab in patients with advanced or metastatic kidney and liver cancer.

About SRF388:
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver, kidney and lung cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immuno-suppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of hepatocellular carcinoma from the FDA.

About the SRF617-101 Clinical Trial:
The trial is a Phase 1, open-label, multicenter, first-in-human dose-escalation trial of SRF617, a monoclonal antibody that binds and inhibits CD39 activity, in patients with advanced solid tumors. The monotherapy dose escalation portion of the study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of SRF617 as a monotherapy in patients with advanced solid tumors. The monotherapy tumor biopsy expansion portion of the study will further evaluate the safety and intratumoral PD of SRF617 as a monotherapy. The combination therapy dose escalation portion of the study will evaluate the safety, tolerability, PK and preliminary efficacy of SRF617 in combination with gemcitabine + albumin-bound paclitaxel (Abraxane), or SRF617 in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors.

About SRF617:
SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39 in the tumor microenvironment, allowing for a dual mechanism of action to promote anti-tumor immunity via reduction of immunosuppressive adenosine in addition to increasing levels of immunostimulatory ATP. A substantial body of research supports a role for CD39 in allowing cancer to evade immune responses. For example, pancreatic cancer stromal cells within the tumor micro-environment express high levels of CD39 which may inhibit anti-cancer immune responses. In preclinical studies, SRF617 has exhibited strong affinity for and inhibition of CD39, the ability to reduce adenosine and increase ATP levels and anti-tumor activity both as a single agent and in combination with multiple therapeutic agents. SRF617 has been granted Orphan Drug designation for the treatment of advanced pancreatic cancer by the FDA.

On June 4, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported a clinical trial collaboration with Roche to evaluate SRF388, Surface’s investigational anti-IL-27 antibody, in combination with Roche’s atezolizumab and bevacizumab in patients with treatment-naïve hepatocellular carcinoma (HCC) (Press release, Surface Oncology, JUN 4, 2021, View Source [SID1234583559]).

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Atezolizumab plus bevacizumab has been shown to significantly improve overall survival and, as reflected in many global clinical practice guidelines, is the new standard of care for unresectable or metastatic HCC. Evolving preclinical and epidemiologic data suggest a significant role for the immunosuppressive cytokine IL-27 in HCC and in resistance to PD-1 pathway blockade. Therefore, the addition of SRF388 to the proven efficacy of the atezolizumab/bevacizumab regimen has the potential to further improve outcomes in this challenging disease.

"At Surface, we are committed to identifying and accelerating the delivery to patients of life-changing treatments, whether as a single agent or in scientifically and clinically appropriate combinations," said Alison O’Neill, M.D., chief medical officer at Surface Oncology. "This collaboration leverages Roche’s deep experience in hepatocellular carcinoma and Surface’s commitment to rationally and rapidly develop SRF388, a first-in-class antibody against IL-27, to provide meaningful benefit to patients with liver cancer."

About SRF388:
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver and kidney cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of hepatocellular carcinoma from the FDA.

On June 4, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, reported that positive interim Phase 1 data from the Company’s FT516 program for patients with relapsed / refractory B-cell lymphoma at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held virtually June 4-8, 2021 (Press release, Fate Therapeutics, JUN 4, 2021, View Source [SID1234583558]). FT516 is the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The ongoing Phase 1 dose-escalation study of FT516 is currently enrolling patients in the fourth dose cohort of 900 million cells per dose.

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As of the data cutoff date of March 11, 2021, four patients in the second dose cohort of 90 million cells per dose and seven patients in the third dose cohort of 300 million cells per dose were evaluable for assessment of safety and efficacy. Eight of eleven patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria (see Table 1). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy.

"These additional data from our Phase 1 study of FT516 administered off-the-shelf in the outpatient setting continue to reinforce its differentiated safety profile and underscore its potential clinical benefit," said Wayne Chu, M.D., Senior Vice President of Clinical Development of Fate Therapeutics. "Based on the favorable therapeutic profile of FT516 that continues to emerge and the potential to treat patients on-demand without delay, we plan to initiate multiple indication-specific, dose-expansion cohorts for patients with B-cell lymphomas to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including those used as standard-of-care in earlier-line settings."

The ongoing Phase 1 clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single-dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting.

Safety Data
No dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events (TEAEs) of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were reported by investigators (see Table 2). All Grade 3 or greater TEAEs were consistent with lympho-conditioning chemotherapy and underlying disease. Of note, a Grade 3 or greater TEAE of infection was reported in one patient only. There were no discontinuations due to adverse events, and no patients withdrew from the study except in the setting of disease progression. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without the need for patient matching.

Activity Data
As of the data cutoff date of March 11, 2021, eleven relapsed / refractory patients in the second and third dose cohorts were evaluable for assessment of safety and efficacy. Of the eleven patients, nine patients completed both FT516 treatment cycles and eight patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria. Notably, two of four patients previously treated with autologous CD19 CAR-T cell therapy achieved a complete response. Two patients showed progressive disease following the first FT516 treatment cycle and discontinued treatment. The Company previously reported that two patients treated in the first dose cohort (30 million cells per dose) showed progressive disease.

Patient Case Study
The ASCO (Free ASCO Whitepaper) presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months’ duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. Subsequent to the data cutoff date of March 11, 2021, the patient completed a second FT516 treatment cycle after which the response assessment continued to show complete response.

As of March 11, 2021 database entry. Data subject to source document verification.
CR = Complete Response; PR = Partial Response; PD = Progressive Disease
CAR = Chimeric antigen receptor; DH/DE = Double-hit / double expressor; DLBCL = Diffuse large B-cell lymphoma; FL = Follicular lymphoma;
Gr = Grade; HGBCL = High-grade B-cell lymphoma; iNHL = Indolent non-Hodgkin lymphoma; TH = Triple-hit; Transformed iNHL = Aggressive B-cell lymphoma transformed from indolent non-Hodgkin lymphoma
1 Cycle 2 Day 29 protocol-defined response assessment per Lugano 2014 criteria
2 Subject did not proceed to Cycle 2
3 Confirmed DLBCL (transformation from Gr3A FL) subsequent to the data cutoff date of March 11, 2021
4 Cycle 2 Day 29 protocol-defined response assessment reported subsequent to the data cutoff date of March 11, 2021

CRS = Cytokine Release Syndrome; DL = Dose Level; GvHD = Graft vs. Host Disease; ICANS = Immune Cell-Associated Neurotoxicity Syndrome;
M = Million; SAE = Serious Adverse Event; TEAE = Treatment-Emergent Adverse Event
1 Includes two subjects in the first dose cohort of 30 million cells per dose

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Scientists from the Company have shown in a peer-reviewed publication (Blood. 2020;135(6):399-410) that hnCD16 iPSC-derived NK cells, compared to peripheral blood NK cells, elicit a more durable anti-tumor response and extend survival in combination with anti-CD20 monoclonal antibodies in an in vivo xenograft mouse model of human lymphoma. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

On June 4, 2021 Bristol Myers Squibb (NYSE: BMY) reported that the company will participate in a fireside chat at the Goldman Sachs 42nd Annual Global Healthcare Virtual Conference, which will be webcast on Thursday, June 10, 2021 (Press release, Bristol-Myers Squibb, JUN 4, 2021, View Source [SID1234583557]). Chris Boerner, Ph.D., Executive Vice President, Chief Commercialization Officer and Samit Hirawat, M.D., Executive Vice President, Chief Medical Officer, Global Drug Development, will answer questions about the company at 9:40 a.m. ET .

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Investors and the general public are invited to listen to a live webcast of the session at View Source An archived edition of the session will be available later that day.

On June 4, 2021 Ribon Therapeutics, a clinical stage biotechnology company developing therapeutics targeting stress support pathways, reported that positive interim clinical data from the dose escalation portion of its first-in-human Phase 1 trial evaluating RBN-2397, a small molecule inhibitor of PARP7, as a monotherapy in patients with advanced solid tumors (Press release, Ribon Therapeutics, JUN 4, 2021, View Source [SID1234583556]). Presenting the data in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 4, 2021, will be Gerald S. Falchook, M.D., Director, Drug Development, Sarah Cannon Research Institute at HealthONE, Denver, CO and Clinical Investigator in the RBN-2397 Phase 1 trial.

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"We are pleased to see demonstration of target inhibition and preliminary signs of antitumor activity in this early stage of clinical development of a novel target," said Dr. Falchook. "In the expansion part of the study, we will seek to demonstrate definitive clinical activity in tumor types predicted to respond to RBN-2397."

The primary objectives of the study are to determine any dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and establish the recommended phase 2 dose (RP2D). The dose escalation portion evaluated two dosing schedules with multiple ascending dose cohorts of RBN-2397. As of April 1, 2021, the dose escalation portion of the study, in which 50 patients were enrolled, is complete and the key results are as follows:

Single-agent RBN-2397 was well-tolerated at exposures predicted to be efficacious in preclinical studies
RP2D was 200 mg BID on a continuous dosing schedule
In this heavily pretreated, heterogenous patient population, preliminary antitumor activity was observed with one partial response (PR) in a patient with HR+ breast cancer and nine patients with stable disease (SD) > 4 months
Includes one patient with squamous cell carcinoma of lung (SCCL) who has been on study with SD for 17+ months and 29% tumor shrinkage post data cutoff date and a second SCCL patient with SD for 4+ months and 19% tumor shrinkage
Proof of mechanism demonstrated by increase in tumoral Type I interferon (IFN) response and immune cells after treatment with RBN-2397
Expansion phase is currently enrolling patients in a number of defined cohorts, including SCCL
"These results validate our approach to drug development by targeting cellular stress and modulating the immune system to induce antitumor activity," said Sudha Parasuraman, M.D., Chief Medical Officer, Ribon Therapeutics. "We expect the expansion part of the study to establish proof of concept for RBN-2397 monotherapy and look forward to expanding our development program with the initiation of a Phase 1b/2 combination study with pembrolizumab in SCCL in the second half of 2021."

About RBN-2397

RBN-2397 is an orally available small molecule inhibitor of PARP7 that Ribon Therapeutics is developing for the treatment of solid tumors. PARP7 is upregulated in response to cellular stress, including genomic instability in cancers, and acts as a brake on the cellular stress response by negatively regulating the Type I interferon response. By inhibiting PARP7 in tumor cells, RBN-2397 has been shown to directly inhibit cellular proliferation and restore interferon signaling to stimulate an innate and adaptive antitumor immune response. RBN-2397 is currently in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors (NCT04053673). PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung, or SCCL, which represents approximately 30% of all non-small cell lung cancers.