On June 6, 2022 OREGA Biotech, the biotech company committed to the discovery of novel immuno-oncology targets for cancer immunotherapy, provides an update on its CD39 program: Innate Pharma reported that IPH5201, the CD39 blocking monoclonal antibody developed in collaboration with AstraZeneca, will advance into a Phase 2 clinical trial in lung cancer(Press release, OREGA BIOTECH, JUN 6, 2022, View Source [SID1234615566]).

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About IPH5201 antibody

IPH5201 is a humanized CD39 blocking antibody. OREGA Biotech commenced the CD39 program at its inception in 2010, then entered into an exclusive and worldwide License Agreement with Innate Pharma in 2016. The lead antibody has been further partnered with AstraZeneca in 2018. AstraZeneca conducted a multicenter, open-label, dose-escalation Phase 1 trial in advanced solid tumors (NCT04261075) with IPH5201 alone or in combination with durvalumab (anti PD-L1 antibody).

Jeremy Bastid, Chief Executive Officer of OREGA Biotech, commented "We are very pleased that IPH5201 antibody is now progressing into a Phase 2 trial; this represents a major achievement for our company. Our academic cofounders are also very proud of having been involved in the discovery of the immunoregulatory role of the adenosine pathway in cancer, the components of which are now being targeted in multiple clinical trials".

On June 6, 2022 EpiAxis Therapeutics reported as we return to face-to-face biotech conferences after more than two years of virtual attendance (Press release, EpiAxis Therapeutics, JUN 6, 2022, View Source;utm_medium=rss&utm_campaign=epiaxis-executives-attend-us-biotech-conferences [SID1234615600]).

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Chairman Dr David Fuller is currently representing EpiAxis at the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting in Chicago; while CEO Dr Jeremy Chrisp will attend the BIO International Convention from June 13-16, 2022 at San Diego Convention Center.

The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), the world’s premier oncology gathering, opened in Chicago on June 3 for the first time since 2019, bringing the largest crowd of cancer care leaders together since the start of the pandemic. The 2022 ASCO (Free ASCO Whitepaper) Annual Meeting Program is offering presentations on the latest research in cancer care and extensive networking opportunities. This year’s program will feature over 200 sessions complementing the meeting’s theme: Advancing Equitable Cancer Care Through Innovation.

ASCO organisers said last week more than 36,000 people had registered for the conference and 80% were planning to attend the meeting in person.

"It is great to see ASCO (Free ASCO Whitepaper) return to Chicago and have the opportunity to interact with with industry colleagues again after the COVID-19 pandemic," Dr Fuller said. "Each year, the ASCO (Free ASCO Whitepaper) conference brings together oncologists from all around the globe and is attended by medical, educational and industrial stakeholders involved in the field of oncology worldwide. It’s an invaluable opportunity to share EpiAxis’ epigenetic advances with a highly engaged audience."

Dr Jeremy Chrisp is looking forward to attending the 2022 BIO International Convention later this month. The convention will feature more than 100 interactive sessions across four days, covering a variety of therapeutic areas, business development, digital health, patient advocacy and next generation biotherapeutics.

"We are seeking new investors to advance our pioneering epigenetic program into the clinic and the Bio International Convention will be an excellent opportunity to update the industry on our progress in the epigenetic space," Dr Chrisp said.

"We are looking to continue our discussions with potential pharma partners who are receptive to our novel first-in-class oncology therapeutics. Epigenetics is an emerging and active therapeutic area and offers the prospect of a less toxic cancer treatment by re-programming both cancer and immune cells for superior outcomes.

"Importantly, we believe through face-to-face discussion, the underlying value in our programs can best be communicated. EpiAxis is now moving into the next phase of development and is seeking to raise US $12million (tranched) to take us from lead candidate selection through IND filing and an initial Phase 1/2 dose escalation expansion study."

On June 6, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a leading clinical-stage immunotherapy company, reported new positive data from the company’s pivotal Phase 2/3 trial for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (QUILT 3032) and Phase 2 trial in advanced pancreatic cancer (QUILT 88) (Press release, ImmunityBio, JUN 6, 2022, View Source [SID1234615616]). The results, which were presented during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, demonstrate the strong and diverse growth of ImmunityBio’s immunotherapy platform that includes an IL-15 superagonist (N-803), adenovirus vaccine platform, and engineered off-the-shelf natural killer (NK) cell therapy. Together with the company’s self-amplifying RNA and yeast platforms, and Toll receptor activators, along with clinical progress across a range of highly challenging cancer types and commercial-scale manufacturing capabilities, ImmunityBio believes that it is well positioned to change the paradigm of care in cancer and infectious disease.

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"The theme at this year’s ASCO (Free ASCO Whitepaper) conference finally is about combination therapy and immunotherapy. We have been focused on this approach for the past decade and the trial results we presented at this year’s ASCO (Free ASCO Whitepaper) conference are validation that the approach of harnessing the patient’s immune system with a combination of NK and T-cell activation has clinical benefit," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "We have, at risk, made the investments to build GMP commercial-scale manufacturing for our platforms and are now positioned to launch QUILT trials in earlier first-line, neoadjuvant and even preventative settings."

The data demonstrate a potential new option for BCG-unresponsive non-muscle invasive bladder cancer patients who were treated with Bacillus Calmette-Guérin (BCG) plus N-803 (Anktiva) and the doubling of historic overall survival rates in patients with advanced pancreatic cancer who were treated with the Nant Cancer Vaccine, N-803 (Anktiva, IL-15 cytokine fusion protein), and off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion.

"Collectively, bladder cancer and pancreatic cancer claim more than half a million lives globally each year, with many patients failing to respond to the current standards of care," said Sandeep Bobby Reddy, M.D., Chief Medical Officer at ImmunityBio. "In dozens of studies, we have shown that N-803 proliferates NK and T cells and thus serves as an enhancing secondary boost, augmenting the immunological response when given in combination with BCG or a checkpoint inhibitor. This mechanism of action of inducing trained innate immune memory, through the combination of N-803 and a prime, contributes we believe to the compelling results we’re seeing in these important trials."

The study results presented at ASCO (Free ASCO Whitepaper) are summarized below:

QUILT 3032 BCG-unresponsive NMIBC CIS (Cohort A)
In an oral presentation on June 3, 2022, Principal Investigator Karim Chamie, M.D., Associate Professor of Urology at UCLA, presented the final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary non-muscle-invasive bladder cancer (Abstract #4508).

Link to video presentation on ecancer.org:

View Source

Excellent safety and tolerability profile of N-803 + BCG for CIS

1% treatment-related SAEs
0% immune-related AEs
0% grade 4 and 5 AE
71% Complete remission (CR) rate at anytime
26.6 months median durable complete remission
96% Avoidance of bladder cancer progression at 24 months in responders
91% Avoidance of cystectomy at 24 months in responders
100% Bladder cancer-specific overall survival at 24 months
Favorable & familiar dosing schedule with activity localized to the bladder
QUILT 3.032 is an open-label, three cohort, multicenter Phase 2/3 study of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) and was opened in 2017. The primary endpoint for Cohort A of this Phase 2/3 study is incidence of complete response (CR) of CIS at any time. The U.S. Food and Drug Administration (FDA) previously granted N-803 Breakthrough Therapy and Fast Track designations when used in combination with Bacillus Calmette-Guerin (BCG) for the treatment of BCG-unresponsive NMIBC CIS. On May 23, 2022, ImmunityBio announced that it had submitted a Biologics License Application (BLA) to the FDA for N-803 plus BCG for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without Ta or T1 disease.

QUILT 88 Pancreatic Cancer
The study results were presented on June 4, 2022 by the Principal Investigator Dr. Tara Seery of Hoag Cancer Center in a poster session titled Phase 2 clinical trial of DAMP inducers combined with IL15 superagonist, N-803, and anti–PD-L1 NK cell therapy more than doubles historical overall survival in patients with third- to sixth-line advanced pancreatic cancer (Abstract #4147, Poster #132).

Nant Cancer Vaccine (NCV) more than doubled median OS versus historical OS (Manax ASCO (Free ASCO Whitepaper) GI 2019) of 3 months after >2L
Median overall survival in 3rd line subjects (n=34) was 6.2 months (95% CI: 4.9, 9.8)
Overall survival for ITT population (N=78) of 3rd, 4th and 5th line is 5.8 months (95% CI: 4.0, 6.9)
Treatment-related (TR) SAEs were uncommon (6%), no TR deaths were reported
All treatments were performed as outpatient
Treatment ongoing for 25 patients
"For the first time, we are seeing clinical efficacy of immunotherapy in pancreatic cancer. Lung, Kidney, Head and Neck cancer, melanoma and many other cancers have been successfully treated with immunotherapy, but pancreatic cancer has been left behind in the revolution. Now, with ImmunityBio’s combination immunotherapy there is renewed hope for patients with this dreaded disease," said Dr. Seery. "We are hopeful to be able to present similar results at future ASCO (Free ASCO Whitepaper) conferences in the other cohorts of this trial in which we continue to enroll patients."

QUILT 88 is a Phase 2, randomized, three-cohort, open-label study evaluating the comparative efficacy and overall safety of standard-of-care chemotherapy versus low-dose chemotherapy in combination with PD-L1 t-haNK, N-803, and aldoxorubicin in subjects with locally advanced or metastatic pancreatic cancer (NCT04390399). Each treatment setting, as well as each first- and second-line or later maintenance treatment, will be evaluated independently as Cohorts A, B, and C, respectively, with Cohorts A and B having independent experimental and control arms. The study is expected to enroll 328 subjects across all three cohorts (63 of 80 participants are currently enrolled in Cohort C, third-line or greater). The primary objective of Cohorts A and B is progression-free survival (PFS) per RECIST V1.1, and the objective of Cohort C is overall survival (OS). Secondary objectives include initial safety and additional efficacy measures, including overall response rate (ORR), complete response (CR) rate, durability of response (DoR), disease control rate (DCR), and overall survival (OS).

Currently, four trial sites have been activated: Hoag Memorial Hospital Presbyterian in Orange County, Calif., The Chan Soon-Shiong Institute for Medicine in Los Angeles County, Calif., Avera McKennan Hospital and University Health Center in Sioux Falls, South Dakota, which serves patients in the tri-state area (Iowa, Nebraska and South Dakota); and Astera Cancer Care, East Brunswick, N.J.

On June 6, 2022 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, primarily in genetically defined patient populations, reported that data on AL101 from the Phase 2 ACCURACY study in a poster at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 3-7, 2022 in Chicago, Illinois (Press release, Ayala Pharmaceuticals, JUN 6, 2022, View Source [SID1234615633]).

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The poster at ASCO (Free ASCO Whitepaper) provides updated data from the 4mg and 6 mg AL101 cohorts in the ACCURACY study of the AL101, a selective gamma-secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut) (NCT03691207). The most recent safety efficacy, PK, and PD data from the study is presented. The abstract from this study has been released on the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting website (View Source).

"We are excited to have AL101 featured in the 2022 ASCO (Free ASCO Whitepaper) meeting and are pleased with the very promising safety and efficacy data from ACCURACY," said Gary Gordon, M.D., Ph.D., Chief Medical Officer of Ayala. "ACC is an orphan disease with no approved therapies and patients with Notch mutations have a more aggressive disease course and poorer survival outcomes as compared to patients with Notch wild-type. If approved, we see strong potential for AL101 to provide a much needed treatment option for R/M ACC patients and look forward to further advancing this clinical program."

ACCURACY is an open-label, single-arm, multicenter Phase 2 study to assess the clinical activity of AL101 using radiographic assessments of patients with R/M ACC demonstrating disease progression within 6 months prior to dosing. It is the first ACC study selecting subjects with ACC bearing defined NOTCH-activating mutations. A total of 87 patients were enrolled (all with RECIST v1.1 evaluable disease or bone exclusive disease deemed evaluable by MD Anderson Bone Response criteria) and of these, 77 were evaluable for efficacy. Approximately 90% of the patients had metastatic disease at screening. This was a heavily pretreated patient population with over half having previously received some form of systemic therapy. Preliminary data from the study were announced by Ayala in 2021.

Efficacy Results

In the 4mg dose group, 6 patients (14.6%) had a partial response, 23 (56.1%) had stable disease, for an overall disease control rate of 70.7%
In the 6mg dose group, 3 patients (8.3%) had a partial response, 21 (58.3%) had stable disease and for an overall disease control rate of 66.7%
Fifty six percent of the 4mg cohort patients and 36% of the 6mg cohort patients experienced some degree of tumor regression.
The median progression free survival (PFS) in each of the 4mg and 6mg dose cohorts was 3.7 months but was 6.7 months among the patients who had a partial response
Median overall survival (OS) was 9.3 months in the overall group but 12.1 months among the patients who had a partial response.
Both dose regimens demonstrated substantial inhibition of the NOTCH pathway consistent with previous studies, but the higher dose did not improve the observed outcomes
Safety

AL101 was adequately tolerated with most adverse events being Grade 1 or 2
Among all 87 patients, 54 or 62% had treatment related grade 3 or 4 AEs (49% in the 4mg cohort and 76% in the 6mg cohort).
Dr. Renata Ferrarotto, Associate Professor and Director of Head and Neck Oncology Clinical Research at M.D. Anderson Cancer Center and the principal investigator of the study commented "The anti-tumor activity of AL101 in the ACCURACY study suggests that it is providing benefit to a subset of patients with ACC carrying Notch-activating mutations. We are presenting data for the first time showing that subjects who had a partial response to AL101 had progression free survival that was approximately double that of the group as a whole. This result, together with the high disease control rate observed, underscores the clinical relevance of the outcomes, given the aggressive disease course associated with Notch mutations and the fact that the majority of subjects in this trial were heavily pretreated."

Poster presentation details:

Abstract Title: Results of ACCURACY: A phase 2 trial of AL101, a selective gamma secretase inhibitor, in subjects with recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch activating mutations (Notchmut)
Abstract Number: 6046
Session Title: Head and Neck Cancer
Session Date and Time: Monday, June 6, 2022, 1:15 PM-4:15 PM CDT
A copy of the poster will be available on the Ayala corporate website, following the presentation at ASCO (Free ASCO Whitepaper) on June 6.

About Adenoid Cystic Carcinoma (ACC)

ACC is a rare malignancy of the secretory glands including salivary glands, accounting for about 10% of all salivary gland tumors with an annual incidence of 3,400 in the U.S. There is currently no approved standard of care for patients with recurrent/metastatic ACC. Patients with locoregional disease undergo surgery and radiation therapy, with recurring disease treated by chemotherapy. ACC is an immunologically "cold" tumor that is refractory to chemotherapy, with a recurrence rate of about 60% after initial surgery. The Notch pathway has been determined to be an oncogenic driver of ACC and its dysregulation plays a key role in tumorigenesis and correlates with a distinct pattern of metastasis and a poor prognosis.

About AL101

AL101 is an investigational small molecule Gamma Secretase Inhibitor (GSI) that is designed to potently and selectively inhibit Notch 1, 2, 3 and 4, and is currently being evaluated in the Phase 2 ACCURACY clinical studies in patients with adenoid cystic carcinoma (ACC). AL101 is designed to inhibit the expression of Notch gene targets by blocking the final cleavage step by the gamma secretase required for Notch activation. Ayala obtained an exclusive, worldwide license to develop and commercialize AL101 from Bristol-Myers Squibb Company in November 2017. AL101 was granted U.S. FDA Fast Track Designation and Orphan Drug Designation for the treatment of ACC.

On June 6, 2022 TwinStrand Biosciences, Inc., the pioneer in duplex sequencing technology, reported that the company will present several data sets as part of its sponsorship and participation in the annual Advances in Genome Biology and Technology conference in Orlando on June 6-9, 2022 (Press release, TwinStrand Biosciences, JUN 6, 2022, View Source [SID1234615650]). The studies will highlight advances in TwinStrand’s innovative technology and share recent research that demonstrates the power of duplex sequencing for some of the most demanding applications in clinical and foundational research.

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"At TwinStrand, we continue to make progress and see the impact of our technology in important areas like hematology-oncology, genetic toxicology, and cellular therapies," said Jesse Salk, M.D., Ph.D., TwinStrand’s Cofounder, and CEO. "We are pleased to share this progress with the AGBT community and look forward to forming new collaborations that leverage our highly sensitive and specific Duplex Sequencing technology which has consistently demonstrated its potential as a critical decision support tool in medicine, public health, and other fields of science where high-resolution insights are most impactful."

TwinStrand DuplexSeq AML-29 Minimal Residual Disease (MRD) Assays offer high-sensitivity detection of ultra-low frequency mutations in acute myeloid leukemia (AML) cases. The 29-gene panel covers loci that are mutated in up to 95% of adult AML patients and is several orders of magnitude more sensitive and specific than other next-generation sequencing-based (NGS) MRD assays. TwinStrand is a member of the Foundation for the National Institutes of Health Biomarkers Consortium, which recently launched a program to validate and standardize methods of detecting and quantifying MRD in AML patients.

TwinStrand DuplexSeq Mutagenesis Assays offer a novel NGS-based approach to mutational research that detects, quantifies, and characterizes genome mutagenesis. It is the first NGS technology able to directly measure ultra-rare mutations caused by chemical carcinogens, without requiring biological selection and is applicable in vitro and in vivo. The final output is comprehensive data on induced mutations including frequency, simple spectrum, and trinucleotide signatures. TwinStrand is collaborating with the Health and Environmental Sciences Institute (HESI), the UK branch of the European Environmental Mutagenesis Society (UKEMS), and the US National Institutes of Standards (NIST) to showcase the value of error-corrected NGS for various preclinical research and regulatory applications.

AGBT attendees can learn more about TwinStrand technology in the Escambia suite. The company will share details from its pioneering work and partnerships in the field of genetic toxicology, which has significant implications for future regulatory mutagenicity and carcinogenicity testing. Other data sets will showcase recent applications of TwinStrand DuplexSeq products in acute myeloid leukemia and allogeneic cell therapy, including:

Ultra-Sensitive Duplex Sequencing for Quantifying Multi-Individual Cell Therapy Sub-Population Fractions
Authors from TwinStrand Biosciences and Deverra Therapeutics
Duplex Sequencing for Ultra-Low Frequency Measurable Residual Disease Detection in Adult Acute Myeloid Leukemia
Authors from TwinStrand Biosciences, Fred Hutchinson Cancer Research Center, National Heart, Lung, and Blood Institute – National Institutes of Health, and Children’s Hospital Los Angeles
Duplex Sequencing Reveals Ubiquitous Clonal Hematopoiesis and Complex Donor-Recipient Clonal Dynamics Following Hematopoietic Stem Cell Transplant
Authors from TwinStrand Biosciences and Fred Hutchinson Cancer Research Center
Longitudinal Monitoring of Pediatric Acute Myeloid Leukemia Using Duplex Sequencing of Patient-Specific Panels Reveals Ultra-Low Frequency MRD that Marks Persistent Carcinogenesis and Complex Clonal Evolution
Authors from TwinStrand Biosciences, Fred Hutchinson Cancer Research Center, and University of California San Francisco