On December 14, 2022 Precision Biologics, Inc. ("Precision"), a clinical-stage immunotherapy and targeted oncology company, reported the successful completion of the safety phase and the enrollment of new patients into the expansion of the Phase 2 Clinical Trial Combining Precision Biologics NEO-201 monoclonal antibody with Pembrolizumab (Keytruda) (Press release, Precision Biologics, DEC 14, 2022, View Source [SID1234625285]).

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!

The study is enrolling patients at the National Cancer Institute, part of the National Institutes of Health, Bethesda, MD, with metastatic Non-Small Cell Lung Cancer (NSCLC), Head and Neck Cancers, Endometrial Cancer and Cervical Cancer, who have already been treated with checkpoint inhibitor therapy (including prior Keytruda). (View Source)

This ongoing Phase 2 trial is testing to see if the combining of NEO-201 with Keytruda can reactivate the killing activity once checkpoint inhibitors no longer work alone.

Christina M Annunziata, MD, PhD, Clinical Director of the Women’s Malignancy Branch at the NCI has been working both preclinically and overseeing this ongoing clinical trial.

"In our laboratory, we have been studying how this antibody can be used in various cancer treatments. Based on the main mechanisms of action, we have moved forward with a phase 2 clinical trial in combination with pembrolizumab," said Dr. Annunziata.

NEO-201 is a unique monoclonal antibody with multiple mechanisms of action. It has been shown previously to kill cancer cells expressing its target. Additionally, it has been shown in early clinical trials to reduce immune suppressive cells that may be responsible in diminishing cancer killing activity for drugs like Keytruda.

On December 14, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported the upcoming presentation of mature Phase 2 data evaluating zanidatamab in combination with chemotherapy as first-line treatment for HER2-positive gastroesophageal adenocarcinoma (GEA) at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, taking place in San Francisco, CA and virtually on January 19-21, 2023 (Press release, Zymeworks, DEC 14, 2022, View Source [SID1234625284]).

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!

The GEA cohort of this Phase 2 clinical trial (NCT03929666) was fully recruited as of March 1, 2022 with clinical trial sites in the United States, Canada, Chile and South Korea. Enrollment into the biliary tract cancer and colorectal cancer cohorts of the trial continues. The Phase 2 data in GEA supports zanidatamab development in the Phase 3 HERIZON-GEA-01 study, evaluating zanidatamab in combination with chemotherapy with or without tislelizumab for the first-line treatment of HER2-positive GEA (NCT05152147).

The poster presentation will be available on Thursday, January 19, 2023 on the conference website as well as the Zymeworks website.

Title: Zanidatamab + chemotherapy as first-line treatment for HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA)
Lead Author: Elena Elimova, MD, MSc, Princess Margaret Cancer Center, Toronto, Canada
Abstract: 347
Poster Session A: Cancers of the Esophagus and Stomach and Other GI Cancers

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2 and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks has entered into separate agreements with each of BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercial zanidatamab throughout various counties around world.

On December 14, 2022 Alpha-9 Theranostics Inc., a clinical stage company developing differentiated and highly targeted radiopharmaceuticals with the potential to meaningfully improve the treatment of people living with cancer, reported an oversubscribed $75 million Series B financing (Press release, Alpha-9 Theranostics, DEC 14, 2022, View Source [SID1234625282]). The round was led by Nextech Invest, with participation from Frazier Life Sciences, Samsara BioCapital and Quark Venture in addition to existing investors Longitude Capital and BVF Partners.

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!

Alpha-9 is engineering highly effective, bespoke radiopharmaceuticals for the treatment of solid and hematologic malignancies. These molecules are optimized to selectively deliver radiation to tumor sites while minimizing off-target effects. The Series B funding will support advancement of the company’s five programs into the clinic over the next two years while expanding its early-stage programs.

"We have always believed in the company, its founders, and the potential for radiotherapies to effectively address a wide range of cancers," said David Hirsch, M.D., Ph.D., Chief Executive Officer of Alpha-9. "Our team has done excellent work progressing our pipeline of novel radiopharmaceuticals over the last year, and we are excited to have the support of these top-tier investors. With this new investor partnership, we are well positioned to progress multiple targets into the clinic, harnessing the potential of radiopharmaceuticals to realize more effective treatments for people living with cancer."

Alpha-9’s systematic approach to radiotherapeutic design is fueled by a toolbox of technologies and chemistries, which offers broad potential for expansion into a multitude of oncology targets. Leveraging its founders’ deep expertise in the modification of peptides and small molecules, Alpha-9 tailors each component of its radiopharmaceuticals – binder, linker, chelator and radioisotope – to improve the molecule’s overall performance. The company’s development process includes human imaging and dosimetry studies, which provide early feedback on molecule design. This approach is capital efficient and rapid, resulting in de-risked compounds prior to later-stage clinical evaluation.

"The radiopharmaceutical field has evolved over the past several years, attributable to scientific advances, translational data and strong clinical efficacy," said Melissa McCracken, Ph.D., Partner at Nextech Invest and Alpha-9 Board member. "This new generation of radiopharmaceuticals shows improved tumor uptake with limited off-target exposure, resulting in drugs that have better safety and efficacy profiles in the clinic. We are excited by the progress Alpha-9 has demonstrated and are proud to support expansion of its programs and facilities."

In addition to advancing the clinical pipeline, the Series B will enable Alpha-9 to grow its team to support discovery programs. Furthermore, the company will complete the build-out of its research facilities in Vancouver, BC, which will house the chemistry, biology, translational research and radiochemistry teams, as well as support product formulation. Alpha-9 has also invested in radioisotope supply through agreements with multiple lutetium and actinium partners. The company looks forward to expanding these relationships with the Series B proceeds.

The company, headquartered in both Boston and Vancouver, was founded in 2019 by François Bénard, M.D., Kuo-Shyan Lin, Ph.D., and David Perrin, Ph.D., leading researchers from BC Cancer and the University of British Columbia with deep expertise in the modification of peptides and small-molecules to create novel radiopharmaceuticals.

Melissa McCracken, Ph.D., Partner at Nextech Invest, Patrick Heron, M.B.A., Managing Partner at Frazier Life Sciences, Cory Freedland, Ph.D., Partner at Samsara BioCapital, and Matthew Young, M.B.A., Managing Director at Longitude Capital will join the Alpha-9 Board of Directors, along with Darcy Mootz, Ph.D., Site Head at Amunix, a Sanofi Company (Chief Business Officer prior to sale), who will join as a Board advisor.

On December 14, 2022 Geneos Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCV), reported that a third patient has achieved a complete response (CR) among the first 24 patients (23 evaluable) enrolled in GT-30, an ongoing single-arm open-label multi-center Phase 1b/2a study (Press release, Geneos Therapeutics, DEC 14, 2022, View Source [SID1234625281]). Overall response rate by RECIST 1.1 is 30.4% in the evaluable patients consisting of three complete responses, four partial responses, six stable disease, and ten progressive disease.

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!

GT-30 is evaluating safety, immunogenicity, and efficacy of PTCV (GNOS-PV02 plus plasmid-encoded IL-12) administered in combination with the immune checkpoint inhibitor pembrolizumab, in patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progress on, or are intolerant to, first line tyrosine kinase inhibitors (sorafenib or lenvatinib). HCC is characterized by a low tumor mutational burden and is resistant to immune checkpoint monotherapy in the majority of patients due to the immune-excluded tumor microenvironment.

In addition to the three CRs, a fourth patient is also cancer-free after liver and lung lesions shrank to become fully responsive to surgery and radiation, thereby achieving secondary resectability.

Among all patients to date, there have been no vaccination-related serious adverse events (SAEs). Vaccination-related AEs, mostly injection site reactions, have been transient and mild and all Grades 1 and 2.

The Geneos PTCV approach is distinguished from other cancer vaccine platforms in offering a means to vaccinate virtually all patients with all of their neoantigens, and to do so rapidly. PTCVs are DNA-based rather than mRNA, viral vector, or peptide. Unlike these alternatives, Geneos DNA vaccines have the capacity to include up to 40 neoantigens in each vaccine, and up to 80 neoantigens merely by combining two DNA plasmids for each patient.

The most recent CR, a 72 year old male with stage IVa HCC whose PTCV included 40 neoantigens, highlights the value of vaccinating with as many neoantigens as possible. The patient developed therapeutically useful T cell responses to 38 of the 40 vaccine neoantigens, as confirmed by ELISpot analysis. In contrast to the large neoantigen capacity of Geneos’ PTCVs, a vaccine based on a platform with a limited neoantigen capacity would have had to compromise on the vaccine neoantigens delivered, thereby likely limiting efficacy.

"We were confident going into this study of the potential of Geneos PTCVs to offer a level of efficacy never seen previously with a cancer vaccine," stated Niranjan Sardesai, PhD, president and chief executive officer of Geneos. "This latest complete response confirms just how groundbreaking our approach is, not only among cancer vaccines but more broadly among oncology therapeutics. We know of no other cancer treatment which offers the potential for such profound efficacy, even in patients with advanced cancers, with the side effect profile, as seen to date, of a typical seasonal flu shot," added Dr. Sardesai.

GT-30 Trial of Geneos’ Personalized Therapeutic Cancer Vaccines
In the GT-30 trial, DNA plasmid-encoded personalized therapeutic cancer vaccine (PTCV) together with plasmid-encoded interleukin-12 (pIL12, a T cell-stimulating cytokine) adjuvant are administered via intradermal injection followed by electroporation (EP) in combination with pembrolizumab. The potential utility of this combination was suggested by preclinical studies which demonstrate Geneos’ PTCV to rescue PD-1 in murine tumor therapeutic challenge models. Geneos’ PTCVs have been engineered to drive a strong CD8+ T cell response against the tumor. CD8 cells are the killing machines of the immune system, seeking out and destroying cancer cells, but have been difficult to induce using prior vaccine approaches. Adjuvant pIL12 and EP serve to optimize the effectiveness of peripheral vaccination, and their utility is seen by the effective CD4+/CD8+ T cell responses observed to the delivered neoantigens in the GT-30 patients. Each patient’s PTCV is designed based on their unique tumor neoantigens (abnormal mutations and genomic variations produced by cancer cells), and unlike for other personalized platforms, in most every case, Geneos’ PTCVs include all of a patient’s specific neoantigens. This removes any requirement to try to pre-select the "high value" neoantigens accurately and, instead, leaves it to nature to decide which ones will matter for triggering the desired immune response. PTCV manufacturing "needle to needle" time, i.e. from biopsy to treatment, is six to eight weeks and is in process of being reduced to three to four weeks.

Based on the full 24-patient data, which were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting last month, Geneos has expanded GT-30 to enroll a further 12 patients, with first reports on benchmark overall survival (OS) from the full cohort of 36 anticipated in mid-2023. In parallel, the company is developing plans with its medical advisors for a potential registrational trial in advanced HCC and preparing for discussions with regulatory agencies.

On December 14, 2022 Sirnaomics Ltd. (the "Company" or "Sirnaomics", stock code: 2257.HK), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, reported the interim results of part-one of an ongoing Phase IIb clinical trial of STP705 for the treatment of Cutaneous Squamous Cell Carcinoma In Situ (isSCC) (Press release, Sirnaomics, DEC 14, 2022, View Source [SID1234625280]). The interim results showed that the majority (78%) of 32 patients with STP705 treatment achieved histological clearance. One of the three treatment cohorts achieved 89% histological clearance. STP705 is an siRNA (small interfering RNA) therapeutic that takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down bothTGF-β1 and COX-2 gene expression.

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!

The two-part, double-blind, randomized, placebo-controlled Phase IIb study is designed to evaluate the safety and efficacy of various doses of STP705, administered as an intralesional injection in subjects with isSCC. In the part-one of the study, we have treated 32 patients with 30 μg/ml, 60 μg/ml and 90 μg/ml of STP705, respectively, and 12 patients with 0 μg/ml placebo weekly. After six-week repeated dosing, we collected tissue samples from the treatment sites followed by histological analysis.

This interim report is specifically for part-one of the study results with a total of 44 patients. Based on our Phase IIb study plan, part-two of this study will include 60 additional subjects who will receive selected doses or placebo for a total of more than 100 subjects. Enrolled subjects will be randomly allocated to receive STP705 or placebo injection once a week for a total of six weeks. In the seventh week, the lesion will be excised.

"The positive clinical readouts of the part-one study of this Phase IIb trial provide a further validation of our STP705 for treatment of non-melanoma skin cancers." said Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics. "With more clinical results from this study and the cutaneous Basal Cell Carcinoma (BCC) study (Sirnaomics News Release at PR Newswire, August 29, 2022), we feel more enthusiastic about this novel RNAi cancer therapeutics for treatment of Squamous Cell Carcinoma (SCC), addressing a broader unmet patient need."

"In our study thus far, patients who received various doses of STP705 over six weeks achieved better histological clearance of isSCC excised lesions than the patients who received a placebo," said Dr. Michael Molyneaux, M.D., Executive Director and Chief Medical Officer of Sirnaomics. "As we move into the latter phase of the clinical trial, we will use this information to determine which doses we deem most effective for treating SCC, which is a type of nonmelanoma skin cancer that affects millions of people in the U.S. Currently, there are only a small number of approved non-surgical treatments that exist for SCC."

This interim report of unblinded results of part-one of the Phase IIb study showed that 25 of 32 subjects with STP705 treatment resulted in a high ratio (78%) of histological clearance. Among three treatment cohorts, the 30 μg treatment group (N = 9) achieved the highest histological clearance (89%), while the 60 μg treatment group (N = 12) achieved 75%, and the 90 μg group (N = 11) achieved 73%, which are clearly higher than the placebo group (N = 12) which achieved 58%. There were no treatment-related AE’s or SAE’s and Local Skin Response Scores were stable or improved across all treatment groups.

About Non-melanoma Skin Cancer

Non-melanoma skin cancers (NMSC) are the most common forms of human neoplasia. NMSC constitute a large group of skin cancers that are not melanoma, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Extramammary Paget’s Disease (EMPD), Merkel cell carcinoma (MCC), and skin adnexal carcinomas. Among these, BCC and SCC account for the majority of NMSC with more than 5 million newly diagnosed cases estimated to occur in the U.S. every year. Along with BCC, SCC is one of two major subtypes of NMSC. NMSC treatment market in the U.S. is expected to increase from US$6.5 billion in 2020 to US$22 billion in 2030. In China, the market size of NMSC treatment was US$38 million in 2020 is also expected to grow faster in the coming years, reaching US$149 million in 2030.

A World Health Organization authorized report from "International Agency for Research on Cancer" (2019) has demonstrated that the number of deaths in 2018 globally for both men and women from NMSC is 65,155, where the mortality of Asia NMSC subjects represents 41.9% of the global total, which is significantly more than other individual areas.

Surgery is currently the most common treatment option for the treatment of NMSC. The various forms of surgical modalities carry significant cutaneous adverse events, risk of scar, infection and bleeding. As a result, there is a high unmet need for an FDA approved local injection therapy that is safe and effective.

About STP705

Sirnaomics’ leading product candidate, STP705, is a siRNA (small interfering RNA) therapeutic that takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression. The product candidate has received multiple IND approvals from both the U.S. Food and Drug Administration (FDA) and the Chinese National Medical Products Administration (NMPA), including treatments of cholangiocarcinoma, non-melanoma skin cancer and hypertrophic scar. STP705 has also received Orphan Drug Designation for treatment of cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC). STP705 is currently in seven clinical trials for different indications: a Phase IIb for squamous cell carcinoma in situ (isSCC), a Phase II for basal cell carcinoma (BCC), a Phase I/II for keloid scarring, a Phase I/II for hypertrophic scar (HTS), a Phase I/II for facial isSCC, a Phase I for liver cancer (basket), and a Phase I for medical aesthetics treatment.