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Agenus Data at CTOS 2022 Highlight Durable Clinical Responses of Botensilimab / Balstilimab Combination in Advanced Sarcoma

On November 17, 2022 Agenus (Nasdaq: AGEN), an immuno-oncology company with a broad pipeline targeting cancer and infectious disease, reported that expanded data from the Company’s Phase 1 study of botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) in patients with advanced sarcoma (Press release, Agenus, NOV 17, 2022, View Source [SID1234624210]). The data demonstrate that the combination offers strong durability and superior efficacy compared to what has been reported in separate trials for standard of care and other investigational therapies in sarcoma, including in sarcoma subtypes historically unresponsive to immunotherapy. The results will be presented tomorrow in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting in Vancouver, BC, Canada.

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"The superior efficacy and durable responses achieved with botensilimab and balstilimab in advanced sarcoma build on the unprecedented clinical responses we have observed with this combination in multiple cold, treatment-resistant cancers," said Steven O’Day, MD, Chief Medical Officer at Agenus. "We are advancing multiple randomized Phase 2 trials to evaluate the therapeutic potential of this agent across a range of solid tumors."

Study Design and Highlights:

A total of 13 evaluable patients with advanced sarcoma received either 1 or 2 mg/kg botensilimab every 6 weeks and 3 mg/kg balstilimab every 2 weeks.

Patient Demographics:

Heavily pre-treated, with a median of 3 prior lines of therapy
31% had received prior immunotherapy
82% had a known tumor mutation burden of less than 10 mutations per megabase
Majority were PD-L1 negative by IHC
All of these biomarkers are associated with poor response to immunotherapy.

The botensilimab/balstilimab combination produced superior responses and strong durability relative to what has been reported in separate trials for standard of care and other combinations currently in development.

Objective responses:

46% overall response rate
Other PD-(L)1 + CTLA-4 combinations in a comparable patient population achieved only 12-16% response rates1,2
69% disease control rate (complete response + partial response + stable disease)
Durability:

67% objective responses ongoing at data cut-off
Median duration of response has not been reached
Survival:

12-month overall survival of 77%
Median overall survival has not been reached
Patient Sub-Populations:

Objective response rate of 56% and disease control rate of 78% in 9 patients with angiosarcoma, including 3 of 4 patients with visceral angiosarcoma
Other PD-(L)1 + CTLA-4 combinations achieved only 20-25% response rates in patients with angiosarcoma, with no reported responses in 7 patients with visceral angiosarcoma2,3
Responses observed in additional patients with sarcoma subtypes historically resistant to immunotherapy, including liposarcoma with leiomyosarcomatous differentiation
Tolerability:

Botensilimab was well tolerated; no grade 4 or 5 treatment-related adverse events in this cohort
Safety profile similar to what has been previously reported in the Phase 1 botensilimab program, with no new immune-mediated safety signals observed
"At present, available treatments for advanced soft tissue sarcoma patients only have modest activity, and response rates for other immunotherapy combinations for most types of sarcoma are well below 20 percent," said Breelyn Wilky, MD, Principal Investigator and Director of Sarcoma Medical Oncology at the University of Colorado School of Medicine. "The clinical responses demonstrated by botensilimab and balstilimab in this study are compelling and support plans for further development of this combination in sarcoma."

Presentation Details:

Abstract Number: 1294633

Abstract Title: Results from a Phase 1a/1b Study of Botensilimab (a Novel CTLA-4 Engager) Plus Balstilimab (Anti-PD-1 Antibody) for the Treatment of Patients with Advanced Sarcomas

Presenting Author: Breelyn A. Wilky, MD, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research, University of Colorado Cancer Center

The data will be presented on November 18th at 4:15 PM PDT in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting in Vancouver, BC, Canada. An archived version of the presentation will be available on the Agenus website at agenusbio.com.

RAPT Therapeutics Announces Proposed Public Offering of Common Stock

On November 17, 2022 RAPT Therapeutics, Inc. (Nasdaq: RAPT) ("RAPT" or the "Company"), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, reported that it has commenced an underwritten public offering of $75 million of its common stock (Press release, RAPT Therapeutics, NOV 17, 2022, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-announces-proposed-public-offering-common-0 [SID1234624207]). In addition, RAPT expects to grant the underwriters a 30-day option to purchase up to an additional $11.25 million of its common stock on the same terms and conditions. All of the shares of common stock are being offered by RAPT. The proposed offering is subject to market conditions, and there can be no assurance as to whether or when the proposed offering may be completed or as to the actual size or terms of the proposed offering.

J.P. Morgan, Evercore ISI, Guggenheim Securities and Cantor are acting as joint book-running managers for the proposed offering.

The offering is being made pursuant to a shelf registration statement, including a base prospectus, filed by RAPT with the Securities and Exchange Commission (the "SEC"), which was declared effective by the SEC on November 16, 2020. The offering may be made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. When available, electronic copies of the preliminary prospectus supplement and the accompanying prospectus may also be obtained from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected] or by telephone at (866) 803-9204; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, NY 10055, by telephone at (888) 474-0200, or by email at [email protected]; Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544 or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 6th Floor, New York, New York 10022, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

PureTech to Present at Two Upcoming Investor Conferences

On November 17, 2022 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to changing the treatment paradigm for devastating diseases, reported that members of the management team will participate in fireside chats at two upcoming investor conferences (Press release, PureTech Health, NOV 17, 2022, View Source [SID1234624206]). Webcasts of the presentations will be available at View Source

Piper Sandler 34th Annual Healthcare Conference

Evercore ISI 5th Annual HealthCONx Conference

Northwest Biotherapeutics Reports Positive Top-Line Results From Phase 3 Trial of DCVax®-L for Glioblastoma

On November 17, 2022 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that in its Phase III clinical trial both median survival and the "long tail" of extended survival were increased in both newly diagnosed and recurrent glioblastoma brain cancer patients treated with DCVax-L (Press release, Northwest Biotherapeutics, NOV 17, 2022, View Source [SID1234624205]). The trial has met both the primary and the secondary endpoint under the Statistical Analysis Plan for the trial.

The trial results were reported today in a featured publication co-authored by more than 70 physicians from leading institutions across the U.S., Canada, U.K. and Germany, in the peer reviewed cancer journal JAMA Oncology, entitled "Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination with Extension of Survival Among Patients with Newly Diagnosed and Recurrent Glioblastoma". View Source

The Company believes this is the first time in nearly 20 years that a Phase III trial of a systemic treatment has shown such survival extension in newly diagnosed glioblastoma, and the first time in nearly 30 years that a Phase III trial of any type of treatment has shown such survival extension in recurrent glioblastoma.

Ms. Powers, CEO of NW Bio, commented: "We are excited to see the meaningful survival extensions in glioblastoma patients treated with DCVax-L in this trial – particularly in the "long tail" of the survival curve, where we see more than double the survival rates as with existing standard of care. With well over 400 clinical trials for glioblastoma having failed over the last 15 years, it is gratifying to be able to offer new hope to patients who face this devastating disease."

"It is especially encouraging to see these survival extensions with a treatment that has such a benign safety profile" Ms. Powers continued. "Over 2,100 doses of DCVax-L were administered during the trial, and we found that the adverse event profile was not meaningfully different than with standard of care alone. DCVax-L is also quite simple for the physician and patient: just an intradermal injection in the upper arm, 6 times over the course of year 1, and then twice a year for maintenance thereafter."

Glioblastoma is the most common and most lethal form of primary brain cancer. Standard of care (SOC) treatments have been virtually unchanged for nearly 20 years. With SOC treatments, patients typically survive for only about 15-17 months from diagnosis, with the tumor recurring at about 6-8 months from diagnosis and the patients typically surviving for about 7-9 months after recurrence. Five-year survival from diagnosis is only about 5%.

In the Phase III trial of DCVax-L, median Overall Survival (mOS) for newly diagnosed GBM patients (n=232) was 19.3 months from randomization (22.4 months from surgery) with DCVax-L vs. 16.5 months from randomization in the controls (HR=0.80, p=0.002). Survival at 48 months from randomization was 15.7% vs. 9.9%, and at 60 months was 13% vs. 5.7%. For recurrent GBM (n=64), mOS was 13.2 months from relapse vs. 7.8 months (HR = 0.58, p<0.001). Survival at 24 and 30 months post-recurrence was 20.7% vs. 9.6%, and 11.1% vs 5.1%, respectively. In newly diagnosed GBM patients with methylated MGMT, mOS was 30.2 months from randomization (33 months from surgery) with DCVax-L (n=90) vs. 21.3 months in controls (n=199) (HR=0.74, p=0.027).

From a safety perspective, out of more than 2,100 doses of DCVax-L administered during the Phase III trial, there were only 5 serious adverse events that were deemed at least possibly related to the treatment. There were 3 cases of intracranial edema, 1 case of nausea and 1 case of lymph node infection.

DCVax-L is a fully personalized immune therapy made from a patient’s own immune cells (dendritic cells) and antigens (biomarkers) from a sample of the patient’s own tumor. A multi-year set of doses is produced in a single manufacturing batch, which takes 8 days. The product is then stored frozen in individual doses, and is "off the shelf" throughout the treatment regimen. The doses are stored centrally and simply taken out of the freezer and delivered to the physician when needed for the patient’s next treatment.

Dr. Marnix Bosch, senior author on the publication, concluded "This DCVax-L trial, at 94 hospitals in 4 countries, involved the teamwork of a large number of dedicated investigators. Publication of the results in the prestigious, peer-reviewed journal JAMA Oncology honors this teamwork and demonstrates how the field can move forward with novel therapies and innovative clinical trial designs."

The Company is currently working on preparations for applications for regulatory approval of DCVax-L.

Kyowa Kirin and MEI Pharma Announce Topline Data from the Phase 2 MIRAGE Study Evaluating Zandelisib in Patients with Indolent B-cell non-Hodgkin’s Lymphoma in Japan

On November 17, 2022 Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions utilizing the latest biotechnology and MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported topline data from the Phase 2 MIRAGE study evaluating zandelisib, an orally administered investigational phosphatidylinositol 3-kinase delta ("PI3Kδ") inhibitor, in patients with indolent B-cell NonHodgkin’s Lymphoma (iB-NHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) in Japan (Press release, Kyowa Hakko Kirin, NOV 17, 2022, View Source [SID1234624204]).

The data demonstrated a 75.4% objective response rate (ORR) and 24.6% of patients achieved a complete response (CR) as determined by Independent Review Committee (IRRC) assessment (n=61). The data is currently insufficiently mature to accurately estimate duration of response (DOR). With 9.5 months median duration of follow-up, a discontinuation rate due to any treatment emergent adverse event was 14.8%.

"We are very pleased to announce the data from Phase 2 MIRAGE study," said Yoshifumi Torii, Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin. "We continue to see a favorable profile of zandelisib with intermittent dosing that aims to balance efficacy and safety in Japanese patients who have been heavily pre-treated. These results are consistent with the data of the similarly designed TIDAL study already announced in November 2021. We remain committed to maximizing the value of zandelisib in B-cell malignancies with our partner MEI Pharma and bringing hope to lymphoma patients around the world."

"The results from the MIRAGE study announced today are not only consistent with the data from the Phase 2 TIDAL study, but support the potential of zandelisib on the intermittent schedule to also provide a high rate of response and low rate of Grade 3 or greater adverse events in Japanese patients with indolent B-cell non-Hodgkin lymphoma," said Richard Ghalie, M.D., chief medical officer of MEI Pharma.

[MIRAGE Study Details] The MIRAGE study is a multicenter, open-label, single-arm Phase 2 trial evaluating zandelisib as monotherapy for Japanese patients with relapsed or refractory (r/r) iB-NHL who received at least two prior systemic therapies (NCT04533581).

A total of 61 patients were enrolled and the median age of patients was 70 years old. Enrolled patients were generally heavily pretreated; the median number of prior therapies was 3 (range 2-9). The primary efficacy endpoint is ORR as assessed by IRRC using a modified Lugano criteria. Patients were administered zandelisib 60 mg once daily for two 28-day cycles as response induction therapy, followed thereafter by 60 mg once daily dosing for the first seven days of each subsequent 28-day cycle, a schedule called Intermittent Dosing Therapy. Efficacy The primary endpoint of ORR of zandelisib as a single agent was 75.4% (95% CI [62.7, 85.5]), as assessed by IRRC; the complete response rate was 24.6% (95% CI [14.5, 37.3]). As of the data cutoff date, the data are not sufficiently mature to accurately estimate the final DOR. Safety and Tolerability With a median follow-up of 9.5 months (95%CI [8.0, 11.1]), 14.8% of patients discontinued therapy due to any treatment emergent adverse event. Grade 3 adverse events of special interest (AESI) were AST and ALT elevation in 8.2% of patients, rash in 3.3%, and 1.6% each for diarrhea, colitis and lung infection.

[Phase 1 Study] We also recently announced the publication of data from the Phase 1 study of zandelisib in Japanese patients with r/r iB-NHL in the International Journal of Hematology (NCT03985189). The publication, entitled "Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin’s lymphoma: an open-label, multicenter, dose-escalation phase 1 study" is available on the journal website. The publication reported a 100% (N=9) ORR and that 22.2% (N=2) of patients achieved CR starting on a continuous daily schedule (45 or 60 mg); patients could be switched to intermittent dosing for an adverse event. No dose-limiting toxicities were observed in the first cycle of therapy, and the maximum tolerated dose was not reached. With 17.5 months median duration of follow-up, zandelisib was generally well tolerated at 60 mg resulting in the recommended phase 2 dose in Japanese patients.

About Zandelisib
Zandelisib, a selective PI3Kδ inhibitor, is an investigational cancer treatment being developed as an oral, once-daily, treatment for patients with B-cell malignancies. Clinical trials are investigating the efficacy and safety of zandelisib as a single agent and in combination with other modalities while administered on an Intermittent Dosing regimen (ID) and in a timelimited manner when dosed in combination. The ID leverages molecular and biologic properties specific to zandelisib. In November 2021, MEI Pharma and Kyowa Kirin announced topline data from ongoing Phase 2 TIDAL study (NCT03768505) evaluating zandelisib as a single agent for follicular lymphoma (FL) patients who received at least two prior systemic therapies.

Zandelisib demonstrated a 70.3% objective response rate (ORR) as determined by an Independent Review Committee (IRRC) assessment in the primary efficacy population (n=91). In addition, 35.2% of patients achieved a complete response. At the time of the data cutoff, the data were insufficiently mature to accurately estimate duration of response (DOR). In line with previously reported data from the Phase 1B study, zandelisib was generally well tolerated. With 9.4 months (range: 0.8-24) median duration of follow-up in the total study population (n=121), interim data demonstrated a discontinuation rate due to any drug related adverse event of 9.9%.

Patients enrolled in the study will continue to be followed for safety and DOR. Other ongoing studies include the Phase 3 COASTAL study (NCT04745832), comparing zandelisib plus rituximab to standard of care chemotherapy plus rituximab in patients with r/r FL or MZL who received more than one prior line of therapy, which must have included an antiCD20 antibody in combination with chemotherapy or lenalidomide. COASTAL, which is also evaluating time-limited intermittent administration of zandelisib, is intended to support marketing applications in the U.S. and globally. In March 2020, the FDA granted zandelisib Fast Track designation for the treatment of adult patients with r/r follicular lymphoma who have received at least two prior systemic therapies.

In November 2021, the FDA granted zandelisib Orphan Drug designation for the treatment of patients with follicular lymphoma. In April 2020, MEI and Kyowa Kirin entered a global license, development, and commercialization agreement to further develop and commercialize zandelisib. MEI and Kyowa Kirin will co-develop and co-promote zandelisib in the U.S., with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the U.S.