On July 18, 2024 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, reported significantly higher PFS for its top responder patient in the Phase 2 study of BriaCell’s Bria-IMT regimen in combination with an immune checkpoint inhibitor in metastatic breast cancer (Press release, BriaCell Therapeutics, JUL 18, 2024, View Source [SID1234645084]). The patient remains alive and she continues to receive BriaCell’s treatment regimen.

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"We are extremely pleased with the unprecedented survival benefit in this very-difficult-to-treat patient," stated Dr. William V. Williams, BriaCell’s President and CEO. "This data represents a step forward in our efforts to build on our knowledge and successes to transform cancer care for patients. We expect to replicate this positive data in our ongoing Phase 3 study and bring relief to cancer patients whose medical needs remain unmet."

"Despite recent advances in cancer therapy, metastatic breast cancer remains an unmet medical need, as current treatments are limited by poor survival and harsh side effects," commented Dr. Giuseppe Del Priore, BriaCell’s Chief Medical Officer. "The Bria-IMT regimen produced a much longer than expected survival benefit in addition to its favorable safety and tolerability in this patient suggesting its potential as a therapeutic option for these cancer patients."

The patient had a large right orbital lesion (behind the right eye) and a right temporal lobe lesion (in the right side of the brain). The temporal lobe lesion is no longer detectable, while the orbital lesion has continued to shrink markedly (see figure showing resolution of proptosis post treatment (small arrows) with reduction in tumor indicated by the large arrows). In addition, her tumor markers (blood tests that correlate with the amount of tumor in the body) have markedly decreased from her pre-treatment levels.

On July 18, 2024 Haystack Oncology, a Quest Diagnostics (NYSE: DGX) company, and Lisata Therapeutics, Inc. (Nasdaq: LSTA), a clinical-stage pharmaceutical company developing innovative therapies for the treatment of advanced solid tumors and other serious diseases, reported a research collaboration (Press release, Lisata Therapeutics, JUL 18, 2024, View Source [SID1234645015]). Lisata will deploy the highly sensitive Haystack MRD technology for the detection of circulating tumor DNA (ctDNA) in a clinical study evaluating certepetide plus chemotherapy as an investigational treatment for metastatic pancreatic cancer.

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In the FORTIFIDE study, Lisata is investigating the safety, tolerability, and efficacy of its lead product candidate, certepetide, when given as a 4-hour continuous infusion in combination with standard-of-care treatment in subjects with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed on FOLFIRINOX, a treatment for pancreatic cancer. As part of this research, Lisata has engaged Haystack to use its MRD technology to measure serum ctDNA levels at multiple timepoints in patients throughout the study as an exploratory endpoint for analyzing the early therapeutic effect of certepetide. Certepetide is an investigational drug designed to activate a novel uptake pathway that allows co-administered or tethered anti-cancer drugs to target and penetrate solid tumors more effectively.

"Our collaboration with Lisata underscores the value of our Haystack MRD technology in helping to drive forward the development of novel treatments for solid tumor cancers," said Dan Edelstein, Vice President and General Manager of Haystack Oncology. "Haystack’s technology was engineered to detect ctDNA with exceptional sensitivity, and we aim to continue to gain insights into ctDNA kinetics via serial measurements as an important and early indication of therapeutic response."

The American Cancer Society estimates more than 66,000 individuals nationwide will be diagnosed with pancreatic cancer in 2024. mPDAC accounts for more than 90% of pancreatic cancer cases and is a highly aggressive form of the disease. Typically, mPDAC advances to this stage because of a lack of early diagnosis or limited patient response to treatments.1

"A significant challenge in the development of anti-cancer therapies for pancreatic tumors is the early measurement of response to treatment. Most clinical trials evaluating pancreatic cancer require waiting for long-term survival outcomes to discern treatment effect," said Kristen K. Buck, M.D., Executive Vice President of R&D and Chief Medical Officer of Lisata. "Conventional response assessment via imaging may lack sensitivity in certain situations, and highly sensitive ctDNA assays offer the potential to quickly identify clinically meaningful biologic activity in difficult to treat cancers. The Haystack MRD test has the level of sensitivity required for us to better identify the selective tumor penetrating effect of certepetide, our lead candidate, for the treatment of solid tumors."

On July 18, 2024 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers (mBC), reported it was granted a U.S. patent that expands its intellectual property portfolio for lasofoxifene, its lead investigational drug (Press release, Sermonix Pharmaceuticals, JUL 18, 2024, View Source [SID1234645004]). The newly issued patent covers methods for treating aromatase inhibitor (AI)-resistant, estrogen receptor-positive (ER+) breast cancer in the absence of ESR1 mutations.

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Evidence of lasofoxifene’s antitumor activity in breast cancers with ESR1 mutations was previously demonstrated during the Phase 2 Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE) trials. In ELAINE-1, lasofoxifene as a monotherapy led to numerically longer progression-free survival than fulvestrant (5.6 vs. 3.7 months; P=0.138) in patients with ESR1-mutated mBC who had progressed after prior CDK4/6i treatment. In ELAINE-2, the combination of lasofoxifene and abemaciclib was associated with a median progression-free survival of approximately 13 months in heavily pre-treated post-CDK4/6i patients with ESR1 mutations. Sermonix is currently enrolling for ELAINE-3, a global registrational Phase 3 study.

The new patent, U.S. Patent No. 12,023,321 B2, titled "Lasofoxifene Treatment of Aromatase-Resistant ER+ Cancer," is based on Sermonix-sponsored research conducted in the laboratory of Dr. Geoffrey Greene, M.D., Ph.D., chair of the Ben May Department for Cancer Research at the University of Chicago. Dr. Greene observed positive findings during a preclinical study examining the effects of oral lasofoxifene in an AI-resistant, ER+ breast cancer model in the absence of ESR1 mutations. Those findings were recently published in the peer-reviewed journal Breast Cancer Research.

"This new patent signals Sermonix’s continued momentum toward the broader study of and potential use of lasofoxifene beyond that in the ESR1-mutated setting, including use in earlier lines of therapy in patients with wild-type (WT) ER," said Dr. David Portman, Sermonix founder and chief executive officer. "There is great medical need for efficacious and well-tolerated new therapies for this large population of breast cancer patients with WT ER who recur in the adjuvant setting or progress in the advanced setting on aromatase inhibitors. We look forward to investigating lasofoxifene’s potential as an effective therapy option for all hormone-treatment resistant breast tumors."

ELAINE-3, with clinical trial sites enrolling across the U.S., Europe, Israel and Canada, is assessing the efficacy of oral lasofoxifene and Eli Lilly and Company’s CDK4/6 inhibitor abemaciclib (Verzenio) compared to fulvestrant and abemaciclib in 400 pre- and post-menopausal women and men with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation.

On July 18, 2024 Agenus Inc. (NASDAQ: AGEN), a leader in developing novel immunological agents to treat various cancers, reported the results of its end-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA), for the advancement of its immunotherapy combination, botensilimab (BOT) and balstilimab (BAL), for the treatment of adult patients with relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC) with no active liver metastases (NLM) (Press release, Agenus, JUL 18, 2024, View Source [SID1234644964]).

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Key Outcomes of the EOP2 Meeting:

Dosing Regimen: Agenus gained agreement on the proposed BOT/BAL combination dosing regimen of 75mg BOT once every 6 weeks for up to 4 doses in combination with 240mg BAL once every 2 weeks for up to 2 years.
Randomized Phase 2 Interim Data: Topline interim data suggest best activity seen at 75 mg BOT/240mg BAL combination (ORR 19.4%; 6-month survival rate of 90%; data continues to mature).
Accelerated Approval: FDA advised against submission of these results in support of an Accelerated Approval based on their view that objective response rates may not translate to survival benefit.
Phase 3 Protocol Design: The FDA recommended the inclusion of a BOT monotherapy arm at Agenus’ discretion in the Phase 3 study.
Dr. Steven O’Day, Agenus’ Chief Medical Officer, stated, "Based on the high level of enthusiasm from significant numbers of global clinical experts and the promising clinical activity we have seen in the Phase 1 and 2 studies, our commitment to seek all possible pathways to make BOT/BAL available to patients is unwavering. This includes exploring opportunities to partner in the U.S. to accomplish a successful Phase 3 trial."

Agenus previously disclosed data from the Phase 1 trial, which showed an overall response rate (ORR) of 23% in the 77 MSS mCRC patients without active liver metastases, with a median follow up of 13.6 months. The estimated 6-month, 12-month and 18-month overall survival (OS) rates were 86%, 71%, and 62%, respectively. The estimated median OS was 21.2 months.

Topline interim data (below) from the Phase 2 trial are showing trends consistent with the Phase 1 study, including an ORR of 19.4% and 6-month survival rate of 90% for the BOT 75mg/BAL combination. The safety profile was manageable and no new signals were observed. Agenus plans to continue future discussions with FDA as the Phase 2 data mature and will present these data in totality at an upcoming medical conference.

Topline Interim Phase 2 Data

BOT + BAL

75 mg

(n= 62)

BOT+BAL

150 mg

(n=61)

BOT

75 mg

(n=38)

BOT

150 mg

(n=40)

SOC

(n=33)

ORR %

(95% CI)

n/nn

19.4*

(10.4, 31.4)

12/62

8.2

(2.7, 18.1)

5/61

0

(0.0, 9.3)

0/38

7.5

(1.6, 20.4)

3/40

0

(0.0, 10.6)

0/33

Follow-Up (m)

Mean (SD)

Range

9.5

(2.77)

1.2, 15.7

9.1

(3.25)

0.1, 16.6

7.8

(4.37)

0.2, 14.8

8.2

(4.53)

0.7, 17.1

5.5

(5.30)

0.0, 13.0

*Pending confirmation of two additional responses in 75mg BOT + BAL arm. No responses are pending confirmation in other arms.

​These results are particularly meaningful, as the landscape of MSS colorectal cancer treatment has seen little advancement leaving a significant gap in effective therapies for patients.

"MSS colorectal cancer, representing approximately 95% of colorectal cancer cases, remains a disease setting with substantial unmet need and is considered to be one of the most challenging types of cancer due to its high incidence and mortality rates," said Michael Sapienza, Chief Executive Officer of Colorectal Cancer Alliance. "The rapidly growing number of diagnoses in younger individuals is particularly alarming. There is an urgent need for new treatment options that can transform the trajectory of MSS colorectal cancer and provide lasting benefits for patients."

In addition to the progress in the U.S., Agenus is advancing its efforts to bring BOT/BAL to patients in Europe. Engagements with the European Regulatory Authority to explore registration paths are scheduled for later this summer. These discussions aim to align on the regulatory path for approval of the BOT/BAL combination in Europe.

Other areas of BOT/BAL clinical development:

Agenus continues to pursue opportunities for BOT/BAL development in earlier lines of CRC and other tumor types where BOT/BAL has demonstrated clinical activity, such as lung, melanoma, and pancreatic cancers. The company expects to present data from some of these programs at future medical congresses, including BOT/BAL in sarcoma at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in September 2024.

About Botensilimab

Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 1100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

About Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, and is estimated to be the number one killer of men aged 50 and above and second leading killer of women in the same age category. Microsatellite stable (MSS) colorectal cancer is the most prevalent form of the disease, representing approximately 95% of patients with colorectal cancer. Survival remains poor for advanced disease, and the burden is shifting to a younger population. Alarmingly, from 1995 to 2019, the number of patients under the age of 55 who were diagnosed with CRC in the United States nearly doubled.

On July 18, 2024 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported that the first patient has been dosed in Pure Biologics’ exploratory Phase 0 clinical study of PBA-0405 (Press release, Twist Bioscience, JUL 18, 2024, View Source [SID1234644963]). PBA-0405 is a fully human IgG1 antibody that was discovered using Twist Biopharma Solutions’ synthetic antibody phage display libraries. Twist Biopharma Solutions, a division of Twist Bioscience, provides an integrated offering of in vitro, in vivo, and in silico tools for antibody discovery research. This exploratory study is designed to provide early insights into the biological effects of PBA-0405 within the tumor environment.

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"Solid tumors are historically difficult for drug developers to target and treat. This is the first antibody identified using our Twist Biopharma Solutions Library of Libraries to be tested in patients and it validates the potential of our synthetic antibody libraries to be used to discover novel drug candidates for hard-to-treat cancer indications," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "This is one of two of Pure’s candidates discovered using our synthetic antibody libraries and we look forward to seeing their progression."

PBA-0405 targets ROR1, a tumor-associated antigen expressed on many solid tumors and B cell malignancies. PBA-0405 is designed to make tumors visible to the immune system, and to induce an immune response by recruiting and activating tumor-killing cytotoxic immune cells.

Pure Biologics’ multi-center, single arm, open-label pharmacodynamic biomarker Phase 0 trial is designed to study the biological effects within the tumor microenvironment of PBA-0405 when administered intratumorally in microdose quantities via the CIVO device. The study will evaluate the pharmacodynamic activity of PBA-0405 in solid tumors including head and neck squamous cell carcinoma, certain subtypes of soft-tissue sarcomas and triple-negative breast cancer. Pure Biologics is conducting the clinical study and holds full responsibility for the development and potential regulatory submission of PBA-0405. ClinicalTrials.gov ID NCT06273852

"With the dosing of the first patient in our exploratory Phase 0 study, PBA-0405 is the first ROR1-targeting compound of its mode of action to enter into studies in patients. We’re encouraged by the preclinical data we’ve seen so far and are eager to evaluate its pharmacodynamic activity in human studies," said Pieter Spee, PhD, Chief Scientific Officer at Pure Biologics. "By working with Twist Bioscience to leverage their synthetic antibody libraries for early-stage discovery, we were able to move quickly to the development stage. We look forward to continuing to advance our pipeline of immuno-oncology antibody candidates and drive toward our goal of delivering first-in-class therapies to patients."

About the Collaboration

PBA-0405 was discovered as part of an ongoing collaboration between Twist Bioscience and Pure Biologics. Under the terms of the agreement announced in 2021, Twist Biopharma Solutions, a division of Twist Bioscience, grants Pure Biologics access to select synthetic antibody phage display libraries derived only from sequences that exist in the human body and further optimized by leveraging state-of-the-art approaches, including artificial intelligence and big data analytics. Certain libraries among the portfolio are deliberately tailored to match chosen classes of biological targets as well as to enhance bispecific antibody forming capabilities. Together, the companies work to discover, validate and optimize new antibody candidates against targets useful for immuno-oncology applications. Pure Biologics will pay Twist annual maintenance fees in addition to future payments for clinical and commercial achievement for any antibodies resulting from the collaboration. The Phase 0 study does not trigger a milestone payment for Twist.