On April 13, 2021 Biomica Ltd., an emerging biopharmaceutical company developing innovative microbiome-based therapeutics and a subsidiary of Evogene Ltd. (NASDAQ: EVGN) (TASE: EVGN), reported additional positive pre-clinical results in its immuno-oncology program demonstrating efficacy of its live biotherapeutic product (LBP) consortium BMC128, this time in melanoma (Press release, Biomica, APR 13, 2021, View Source [SID1234577998]). In these studies, Biomica tested BMC128, which consists of four live bacterial strains, in a mouse model of melanoma.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Elran Haber, CEO of Biomica, stated: "We are very excited with the results of this study demonstrating the effectiveness of BMC128 in treating additional types of solid cancer tumors. These positive pre-clinical results indicate the potential of BMC128 to become best-in-class in the treatment of solid cancer tumors, and help validate Biomica’s computational-based drug design approach. We look forward to providing incremental updates as we work towards a first-in-human, proof of concept clinical trial."

Treatment with BMC128 in combination with Immune Checkpoint Inhibitors (ICI) immunotherapy significantly enhanced anti-tumor activity, resulting in an increased response of melanoma tumors to anti-PD1, as demonstrated in an improved Objective Response Rate (ORR) and Percent Tumor Growth Inhibition (%TGI). The group treated with only anti-PD1 showed no response (ORR = 0%) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST), while the group treated with a combination of BMC128 and anti-PD1 demonstrated a total of 13% response (ORR = 13%). The %TGI was increased by 100% in the BMC128 and anti-PD1 combination treated group compared to the group treated by anti-PD1 alone. Response to BMC128 was correlated with a desired anti-tumor immunological profile. BMC128 changed the course of response to ICI, leading to stimulation of the immune system which shifted cold-tumors into hot-tumors.

These positive results supplement previous pre-clinical data using BMC128 in combination with ICI in a breast cancer mouse model that demonstrated pronounced anti-tumor activity as manifested in an increase of almost 50% in ORR. The current results demonstrate the potential applicability of BMC128 and its relevance to treating multiple types of solid tumors.

Biomica’s immuno-oncology program is based on the premise that the gut microbiome affects the efficacy of cancer immunotherapy, specifically that of the ICI involving the blockade of PD-1 or PD-L1 and CTLA-4 as suggested in scientific literature.[1],[2] Fecal microbial transplantation has been recently reported to increase response in patients resistant to immune-checkpoint therapy[3],[4], however the specific microbial entities driving this response are currently unknown. BMC128 is a rationally-designed microbial consortium identified and selected through a detailed functional microbiome analysis using PRISM, a proprietary high-resolution microbiome analysis platform powered by Evogene’s MicroBoost AI platform.

As previously reported, Biomica has initiated scale-up processes and Good Manufacturing Practice (GMP) production of its drug candidate in its immuno-oncology program in preparation for the first-in-human proof-of-concept clinical trial expected later this year.

Mr. Ofer Haviv, Chairman of Biomica and Evogene President & CEO, stated: "We are proud of the results that Biomica reported today. These results support the computational biology capabilities developed by Evogene and Biomica which predicted that the microbes that make up BMC128 can be utilized to improve the efficacy of ICI in solid tumors. We look forward to validating the same computational forecasting capabilities in additional successful programs led by Biomica such as IBD and IBS."

[1] Zitvogel et al. 2018, Science 359 (6382)
[2] Thompson J, et al. Microbiome & immunotherapy: Antibiotic use is associated with inferior survival for lung cancer patients receiving PD-1 inhibitors. J Thorac Oncol 12(suppl 2):S1998, 2017
[3] Baruch E, et al. 2021. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science, 371 (6529)
[4] Davar D, et al. 2021. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science, 371 (6529)

On April 13, 2021 Iterion Therapeutics, Inc., a venture-backed, clinical stage biotechnology company developing novel cancer therapeutics, reported that it has confirmed the safety of Tegavivint, a novel, potent and selective nuclear beta-catenin inhibitor, after completing enrollment and dosing the final patient in a multicenter Phase 1/2a dose expansion clinical study of Tegavivint in patients with desmoid tumors (Press release, Iterion Therapeutics, APR 13, 2021, View Source [SID1234577997]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Nuclear beta-catenin is a highly-studied oncology target associated with numerous cancer types. Tegavivint is unique among nuclear beta-catenin inhibitors in that it binds to TBL1 (Transducin Beta-like Protein One), a novel downstream target in the Wnt-signaling pathway. As such, Tegavivint enables silencing of Wnt-pathway gene expression without affecting other Wnt/beta-catenin functions in the cell membrane, thus avoiding toxicity issues common to other drugs in this pathway.

The Phase 1/2a clinical trial of Tegavivint in patients with progressive desmoid tumors was designed as an open-label, non-randomized dose-finding study. The primary objectives of the study were to evaluate the safety and tolerability of Tegavivint. Secondary objectives were to determine the durability of response (DOR) to Tegavivint after the achievement of best response. The total study enrolled 24 patients. During the dose expansion portion of the trial 16 of these patients were treated with a recommended Phase 2 dose (RP2D) that was established based on pharmacokinetic exposure levels and clinical responses in a recently completed Phase 1 study.

Data from patients treated in the dose expansion portion of the trial reaffirmed Tegavivint’s safety at the RP2D level. No dose-limiting toxicities or significant adverse events were observed. This data will enable Iterion to accelerate clinical activity in additional cancer indications where nuclear beta-catenin signaling has been identified as a potential therapeutic target, including AML, NSCLC, and certain pediatric cancers. Iterion expects to initiate clinical programs investigating Tegavivint for these indications in 2021.

"We have seen very good tolerability with no dose-limiting toxicities and no significant adverse events in escalating clinical doses," said Casey Cunningham, Chief Medical Officer of Iterion. "We are seeing a very strong safety signal in patients who have been on Tegavivint for over a year and are also observing tumor activity in patients. We continue to follow the patients that are still receiving treatment and look forward to sharing efficacy results at an upcoming medical conference."

Rahul Aras, CEO of Iterion, stated: "The completion of enrollment in the dose expansion phase of our desmoid tumor clinical trial and demonstration of safety and clinical activity at the RP2D represent important milestones in our clinical development of Tegavivint. We look forward to advancing the clinical development of Tegavivint in desmoid tumors as this disease target is greatly underserved. The results of this study also provide a ‘green light’ to initiate clinical development of Tegavivint in additional, high-value cancer settings, including AML, NSCLC, and certain pediatric cancers, that are characterized by nuclear beta-catenin overexpression."

About Desmoid Tumors

Desmoid tumors are rare, non- metastasizing sarcomas that overexpress nuclear beta-catenin, a historically "undruggable" oncology target implicated in cell proliferation, differentiation and immune evasion. An estimated 1,500 patients in the US are newly diagnosed with desmoid tumors each year. Desmoids are most commonly diagnosed in young adults between 30-40 years of age and are associated with significant morbidities, including severe pain, disfigurement, internal bleeding and organ damage, range of motion loss and, in rare cases, death. Iterion has received Orphan Drug Designation for Tegavivint to treat desmoid tumors, a disease for which there are no FDA approved therapies.

On April 13, 2021 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported that Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin, will host a conference call and webcast on Thursday, April 29, at 4:30 p.m. ET to discuss first quarter 2021 financial results and provide a general business update (Press release, BioMarin, APR 13, 2021, prnewswire.com/news-releases/biomarin-to-host-first-quarter-2021-financial-results-conference-call-and-webcast-on-thursday-april-29-at-430pm-et-301266955.html [SID1234577996]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Interested parties may access a live audio webcast of the conference call via the investor section of the BioMarin website, www.biomarin.com. A replay of the call will be archived on the site for one week following the call.

On April 13, 2021 Qilu Puget Sound Biotherapeutic Corp. (Sound Biologics), an emerging biotechnology company focused on developing a novel MabPair platform for antibody-based combination therapies for the treatment of cancer, inflammation and autoimmune disease, reported a clinical update on its first MabPair product PSB205 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Sound Biologics, APR 13, 2021, View Source [SID1234577995]). Dr Li Zhang of Sun Yat-Sen University Cancer Centre (SYSUCC), Guangzhou, China presented a poster on Phase 1 Clinical Trial results of PSB205, a combination of anti-PD1 and anti-CTLA-4 antibodies that are manufactured together as a single product, in patients with advanced malignant tumors. The study is sponsored by Qilu Pharma in China.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Details of the presentation:

Presentation Title: Development and Preliminary Clinical Activity of QL1706 (PSB205), a Combination of anti-PD1 and anti-CTLA-4 Antibodies Manufactured Together as a Single Product

Session Title/Category: Phase I Clinical Trials

Session Type: E-Poster Session, 8:30 AM – 11:59 PM, Saturday, April 10

Poster Number: CT119

Forty-seven patients, 95% of whom had refractory Naso-Pharyngeal (NPC) or lung (NSCLC) cancers, were enrolled at a single clinic with over 5 ascending dose levels in a standard 3+3 design. A dose of 5 mg/kg was selected for continued clinical development. The most common side effects were Grade 1 pruritus and rash. Dose-limiting immune-related reactions occurred only at doses higher than 5 mg/kg. The Overall Rate of Response (ORR) was 29% among 35 patients evaluable for tumor response; among 20 patients without prior exposure to checkpoint-targeted immunotherapy, 40 % achieved Partial Response (PR), whereas 2 of 10 patients (20%) previously treated and progressed on earlier immunotherapy realized PR. For 5 patients on study, pre-study checkpoint inhibitor exposure status was unknown due to earlier participation in a still-blinded randomized immunotherapy trial.

"The Phase 1 data presented at AACR (Free AACR Whitepaper) provides encouraging proof-of-concept and early clinical validation of the MabPair platform," commented Sound Biologics’ Chief Executive Officer Wei Yan, PhD. "The early data offer multiple opportunities for further development of this dual immune checkpoint blockade product."

About PSB205

PSB205 is a first-in-class bifunctional product that contains a mixture of unique anti-PD-1 and anti-CTLA-4 monoclonal antibodies produced by a single cell line via the company’s proprietary MabPairTM technology. MabPair products offer many advantages over bispecific antibodies. The relative ratio of the two antibodies in the MabPair can be well controlled, and each antibody is individually engineered for optimal target coverage, effector function, pharmacokinetics and exposure. The anti-CTLA-4 component of the MabPair is designed with a shorter half-life than currently available anti-CTLA-4 antibodies in an effort to reduce known side effects associated with CTLA-4 blockade. Preclinical studies with PSB205 demonstrated superior efficacy in tumor models compared to either checkpoint inhibitor alone. PSB205 represents a potentially best-in-class immuno-oncology product that promises to exhibit robust combination activity while being significantly more tolerable to patients than currently approved anti-PD-1/anti-CTLA-4 combinations. Parallel Phase 1 studies in a broad range of refractory solid tumors are currently ongoing in China and the United States (www.clinicaltrials.gov; NCT03986606), and the AACR (Free AACR Whitepaper) poster represents the first release of clinical data from one of these studies.

On April 13, 2021 HTL , world leader in biotechnology solutions based on hyaluronic acid (HA) and other biopolymers, and Echelon Biosciences Inc. , global supplier of biochemical reagents, tests and Services for US-based Research and Development Laboratories reported a new partnership (Press release, Echelon Biosciences, APR 13, 2021, View Source [SID1234577993]). This partnership concerns the distribution of HA and high quality glycosaminoglycans (GAGs) as well as the development of new GAGs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This collaboration allows university research and pharmaceutical development laboratories to have access to a wide range of products based on hyaluronic acid and glycosaminoglycans (GAG), compliant with good manufacturing practices (GMP). By providing researchers with superior quality, clinical grade products at the early stages of research, the partnership aims to bridge the gap between laboratory research, development and commercialization, and accelerate innovation around the world.

"Innovation is at the heart of HTL’s DNA," said HTL CEO Yvon Bastard . "This line of development is fully in line with our mission and our vision: to provide science today with the means to develop products that will improve health in the world in the future".

"This new partnership provides scientists and researchers with key technologies to develop innovative biopolymer solutions for new medical applications in the fields of aesthetics, ophthalmology, rheumatology, tissue engineering and drug administration, "said Charles Ruban , deputy CEO of HTL. "This is the true meaning of the signature of HTL: ‘Beyond, together’. HTL’s ambition is not only to develop its leading position in the production and distribution of hyaluronic acid around the world, but also to build the solutions of tomorrow based on glycosaminoglycans ".

"With hyaluronic acid and HTL’s other GAG-based products, Echelon is giving itself the opportunity to expand its line of industry-leading HA-based extracellular kits, tests and matrices. HTL is internationally recognized for its production of premium quality biopolymers. Says Bert Israelsen , President of Echelon Biosciences . "Echelon offers its customers access to innovative tools and unparalleled technical support, thereby maximizing creativity in basic and applied research. With its fermentation and organic synthesis platforms, HTL creates functionalities and added value by developing chemically modified biopolymers, targeted for specific needs ".

"This new partnership is an important step in the deployment of HTL in the North American market and to the American medical community," said Glenn Prestwich, Ph.D. , One of the founders of Echelon and today hui expert in science and innovation at HTL. By entrusting Echelon with the distribution of its hyaluronic acid and research glycosaminoglycans products, HTL aims to increase its support and participation in biopolymer research in the United States and globally, as well as its ability to research and development.

"This new initiative is a testament to HTL’s determination to invest in healthcare innovation," said Humberto C. Antunes , HTL strategic advisor and former CEO of Galderma. He added: "In the areas of health and wellness, the biotechnology ecosystem for innovation, incubators and established and emerging companies is incredibly vibrant in the United States, Mexico and Canada. . This means enormous growth potential for HTL’s products ".