On April 14, 2021 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, and Lonza reported that the companies have entered into an agreement for the manufacture of ATYR2810, aTyr’s monoclonal antibody targeting Neuropilin-2 (NRP2) that is currently in preclinical development for cancer (Press release, aTyr Pharma, APR 14, 2021, View Source [SID1234578046]).

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Under the terms of the agreement, Lonza will utilize its Ibex Design, a fully integrated end-to-end program, to manufacture cGMP material for ATYR2810. The agreement will cover the early stages from gene to Investigational New Drug (IND) and will provide both drug substance (DS) and drug product (DP) to support toxicological studies in animals and early clinical development in humans.

The scope will include process support, including cell line development, process development, and supply chain simplification, to DS and DP manufacturing at Lonza’s Visp and Stein (CH) sites.

"As we prepare to advance ATYR2810 to clinical stage development, we are pleased to work with Lonza, a partner with extensive and proven capability in antibody manufacturing, for the production of our first anti-NRP2 antibody," said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. "Having recently initiated IND-enabling activities for ATYR2810 following some compelling preclinical data in triple-negative breast cancer, strengthened by additional data in lung cancer, this agreement with Lonza reflects our commitment to this program and will support our efforts to eventually advance ATYR2810 to in-patient trials in cancer, including certain aggressive tumors where NRP2 is implicated."

"We look forward to supporting aTyr as they advance their novel therapeutic antibody from preclinical stages into the clinic. This collaboration signifies our commitment and flexibility in accommodating the specific and unique needs of small biotech companies," said Jennifer Cannon, Senior Vice President, Global Head of Mammalian Biologics, Lonza.

About ATYR2810

aTyr is developing ATYR2810 as a potential therapeutic for certain aggressive tumors where Neuropilin-2 (NRP2) is implicated. ATYR2810 is a fully humanized monoclonal antibody that is designed to specifically and functionally block the interaction between NRP2 and one of its primary ligands, VEGF. ATYR2810 is the first Investigational New Drug (IND) candidate to arise from aTyr’s in-house research program designing monoclonal antibodies to selectively target the NRP2 receptor and its associated signaling pathways. NRP2 is a cell surface receptor that is highly expressed in certain tumors, in the lymphatic system and on key immune cells implicated in cancer progression. Increased NRP2 expression is associated with worse outcomes in many cancers. Preclinical data suggest that ATYR2810 could be effective against certain types of solid tumors. ATYR2810 is currently undergoing IND-enabling studies.

On April 14, 2021 Samsung Biologics reported that it has signed a consignment development (CDO) contract with Panolos Biosciences for ‘PB101’, a new anti-cancer drug candidate (Press release, Panolos Bioscience, APR 14, 2021, View Source [SID1234656257]).

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Through this contract, Samsung Biologics plans to provide services throughout the CDO process, from cell line development of Panolos ‘PB101’ to process development, clinical sample production and clinical trial plan (IND) submission support, and non-clinical and global clinical material production.

‘PB101′, Panolos’ next-generation anti-cancer drug candidate, targets all families (VEGF-A, VEGF-B, Placental Growth Factor) of VEGF (Vascular Endothelial Growth Factor) that is overexpressed around cancer cells. It acts to inhibit the growth of cancer cells. ‘PB101’ is a substance with high difficulty in research due to its complex protein structure.

Samsung Biologics established a customized development strategy for the success of ‘PB101’ and was once again recognized for its complex protein-based high-level development capability and differentiated expertise.

Lim Hye-seong, CEO of Panolos, said, "’PB101′ is expected to have excellent efficacy as an anticancer and VEGF-related disease treatment by itself, and moreover, the material itself has already proven its value as a platform technology." He continued, "In the future, in the development of multiple target candidates including ‘PB101’, we expect to be able to demonstrate high synergy through close mutual cooperation with Samsung Biologics, which has development capabilities."

Taehan Kim, CEO of Samsung Biologics, said, "We are very pleased to have entered into a partnership with Panolos, which has outstanding potential in the field of protein new drug development. We will do our best to accelerate the development of our client’s materials with the world’s best CDO service provided by our company"

On April 13, 2021 BridgeBio Pharma, Inc. (NASDAQ: BBIO) reported a collaboration with Roswell Park Comprehensive Cancer Center to advance the development of investigational therapeutics for patients with genetically driven cancers (Press release, BridgeBio, APR 13, 2021, View Source [SID1234577968]).

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"We are honored to begin collaborating with Roswell Park, which is renowned for its excellence in cancer research and its mission to set the gold standard for treating patients with genetically driven cancers," said BridgeBio CEO and founder Neil Kumar, Ph.D.

Under the partnership, BridgeBio will work with scientists at Roswell Park Comprehensive Cancer Center to evaluate new research and development opportunities in oncology that have promise to advance and potentially provide clinical benefit for patients. Select therapeutic programs may be pursued by BridgeBio, in close collaboration with Roswell Park Comprehensive Cancer Center scientists, who would remain deeply involved in the ongoing development of these investigational therapies.

"Collaborating with BridgeBio opens up a platform of new resources to support the incredible Roswell Park innovators working on new ways to care for cancer patients with dire unmet need," said Roswell Park Comprehensive Cancer Center President and CEO Candace S. Johnson, Ph.D. "The ability to tap into this network of expertise means greater visibility for our teams and enables a quicker path to the clinic for our most promising ideas and inventions in areas like genetics, bioinformatics and molecular biology."

BridgeBio partners with stand-out academic institutions, including Roswell Park Comprehensive Cancer Center, to support research around genetically driven conditions and is focused on rapidly translating findings into meaningful treatments for patients. Today BridgeBio also announced formal partnerships with Brown University, GlycoNet, The Lundquist Institute, Oregon Health & Science University, University of California, Davis and University of California, San Diego – for a total of 20 partnerships between BridgeBio and leading academic and research institutions to date. For a list of some of the institutions BridgeBio is partnered with, please visit Our Partners page.

With a diverse pipeline encompassing investigational therapies for both rare diseases and genetically validated cancers, BridgeBio provides the insights and support needed to rapidly progress therapeutic research from labs to clinical development. BridgeBio intends to develop similar long-term partnerships based on trust, engagement, science and respect to support its mission of developing life-changing medicines for patients with genetically driven conditions as quickly and safely as possible.

On April 13, 2021 Genetron Holdings Limited ("Genetron Health" or the "Company", NASDAQ:GTH), a leading precision oncology platform company in China that specializes in molecular profiling tests, early cancer screening products and companion diagnostics development, reported the release of 22 research results at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (AACR 2021) (Press release, Genetron Health Technologies, APR 13, 2021, View Source [SID1234577985]).

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The results were from a series of studies that Genetron Health conducted with 13 leading hospitals in China. The Company leveraged original research and innovative technologies such as integrated DNA and RNA sequencing in gene fusion detection, a new MSI (microsatellite instability) detection algorithm model, its "One-Step Seq" method, and core products such as Onco Panscan and comprehensive sarcoma gene detection tests.

These studies analyzed the spread of various types of cancers throughout the Chinese population, covering lung cancer, intestinal cancer, pancreatic cancer, nervous system tumors, thymic carcinoma, and other types of cancers. More specifically, the studies focused on these cancers’ inheritance, mutation, and fusion characteristics. They paid particular attention to the validity of immunotherapy markers for various types of cancers, as well as rare cancer cases and new therapeutic treatments. These studies provided important insights that can enable the accurate diagnosis and treatment of cancer, facilitating the design of effective products in the future.

Dr. Yunfu Hu, Genetron Health’s Chief Medical Officer, said, "Genetron Health is committed to building a strong bridge between scientific research and clinical applications. The studies’ results show that the Company’s innovative technologies and products can help to further analyze the characteristics of cancer genomics for different types of cancer, optimize conventional technologies, and provide ideas for new product design, so as to promote the healthy development of translational medicine. For example, for soft tissue sarcoma (STS), the use of integrated DNA and RNA sequencing in gene fusion detection can greatly improve the detection rate of STS gene fusion, which may benefit more STS patients.

"For hereditary cancers, the screening method used to detect Li-Fraumeni syndrome will also improve cancer detection rates in these patients and provide more intervention opportunities for them; for colorectal cancer, our analysis of KMT2C/2D inactivation mutations is also pointing to more possibilities for immunotherapy patients. And lastly, our work on rare cancer cases and the experimentation of new treatments is furthering the development of diagnosis and treatment research for these various types of patients," Hu added.

Exploring Ways to Optimize Conventional Technologies

To overcome the DNA-sequencing limitations involved with detecting gene fusion, Genetron Health optimized the use of conventional technologies in Study #2288. During this study, more accurate, efficient, and low-cost detection of gene fusion mutations was achieved at the RNA sequencing level. This was evaluated and verified in a STS cohort of 142 Chinese patients. Compared with DNA detection alone, integrated DNA and RNA sequencing improved the detection rate of STS fusion by 177%, which could provide clinical benefits for more STS patients.

Study #2080 optimized the algorithm that detects MSI through next generation sequencing (NGS). The study was conducted on a large cohort of 2,523 samples with various types of cancers. According to the study results, the optimized algorithm was 99.9% consistent with PCR (polymerase chain reaction) testing – the industry’s current gold standard. The positive predictive value of MSI-H was 98.73%, and the negative predictive value of MSS was 99.92%.

Focusing on Hereditary Cancers

Two studies (#1464, #2557) provided screening methods for Li-Fraumeni syndrome, an inherited condition that is characterized by an increased risk for certain types of cancer. These methods utilized in-depth analysis of germline mutations and investigated the distribution of genetic characteristics for pancreatic cancer in the Chinese population, providing evidence and additional ideas for the diagnosis and treatment of hereditary cancers.

Investigating Gene Mutation and Fusion Characteristics

Nine studies (#2217, #2163, #2223, #2216, #2215, #2313, #2252, #2183, #2182) examined the mutation and fusion characteristics of soft tissue sarcoma, melanoma, neuroendocrine tumors, non-small cell lung cancer, thymic carcinoma, small bowel adenocarcinoma, ampullary carcinoma, etc. The studies focused on finding potential targets for precise therapeutic treatment, drug-resistant targets and effective countermeasures.

Probing Immunotherapy Markers

Four studies (#1639, #1640, #1641, #1681) investigated the predictive effects of KMT2C/D loss-of-function mutations, DDR signaling pathway-related gene mutations, ARID1A mutations, and BRCA1/2 mutations on immunotherapy treatments for a wide range of cancer types, providing further insights.

Spotlight on Rare Cancer Cases and New Treatment Therapies

Five studies (#0803, #0422, #1209, #1199, #0625) detected special molecular abnormalities in patients with Lynch syndrome-related lung cancer, metastatic melanoma, anaplastic thyroid carcinoma, papillary thyroid carcinoma and liposarcoma, respectively. In these studies, scientists used molecular detection to diagnose and classify such cancers, and new, targeted therapy and immunotherapy schemes were adopted for these patients, benefiting them in the long run.

Abstract#

Title

1464

Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort

2252

Genome profiling of thymic carcinoma identifies putative driver mutations in the NF-κB signaling pathway

2557

Germline mutation landscape in a large cohort of Chinese pancreatic cancer patients

0803

Molecular diagnosis and immunotherapy of a rare lung carcinoma patient associated with PMS2 c.1144+1G>A mutation-driven Lynch syndrome

0422

Sequential targeted therapy and immunotherapy of a BRAF positive metastatic melanoma patient with BRAF inhibitor vemurafenib, MEK inhibitor cobimetnib and a novel PD-1 antibody Sintilimab

2183

Genomic profiling of small bowel adenocarcinoma reveals targetable mutations in multiple signaling pathways

2217

More somatic mutations can be detected in cerebrospinal fluid ctDNA of NSCLC patients with brain metastases

2182

Evaluation of somatic and germline mutations in ampullary carcinoma reveals actionable targets in multiple signaling pathways

1209

An effective treatment for recurrent and inoperable anaplastic thyroid carcinoma using sintilimab and anlotinib: a case report

1681

Correlation of BRCA1/2 mutations with response to immune checkpoint inhibitors in colorectal cancer

1641

The predictive values of ARID1A mutations for response to immune checkpoint inhibitors are varied in different types of solid tumors

1639

Correlation of KMT2C/D loss-of-function mutations with PD-L1 expression and response to immune checkpoint inhibitors in solid tumors

1640

Correlations of DNA damage response gene alterations with response to immune checkpoint inhibitors are different in solid tumors

2288

Identification of gene fusions in soft tissue sarcoma improved by integrative DNA and RNA sequencing

2163

Molecular characteristics of CDK4 and/or MDM2 amplification in Chinese soft tissue sarcoma (STS) patients

0625

Co-amplification of CDK4 and MDM2 plus HMGA2 fusion in a patient with myogenic differentiation dedifferentiated liposarcoma

2223

Distinct genomic features of cutaneous, acral and mucosal melanomas in a Chinese retrospective cohort

2216

Exploration of the genomic features of pan-neuroendocrine tumors in a Chinese retrospective analysis

2215

Landscape of RET fusion identified by next‑generation sequencing in a Chinese multi-cancer retrospective analysis

1199

Mosaic KRAS G12S mutation associates with poor outcome in papillary thyroid carcinoma: A case report

2080

Tumor microsatellite instability detection method using paired tumor-normal sequence data

2313

The characteristics of ERBB2 exon 20 insertion in a large cohort of Chinese NSCLC patients

On April 13, 2021 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported planned conference presentations scheduled through April and May (Press release, Soligenix, APR 13, 2021, View Source [SID1234578028]). The presentations will focus on the HyBryte (SGX301 or synthetic hypericin) cutaneous T-cell lymphoma (CTCL) program, including elaboration on previously released efficacy and safety outcomes in the Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) study and an update on the CiVax (COVID-19 subunit vaccine) program. Registration links for each conference are included below.

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Planned Oral Presentations:

Visible Light Activated Topical Hypericin Ointment in CTCL: Phase 3 FLASH Study Results presented by Dr. Ellen Kim, Lead FLASH Investigator, at the American Academy of Dermatology Association Virtual Meeting Experience, April 23-25, 2021. As a Top 12 Late-Breaking Research Abstract, Dr. Kim will also be present at a live Q&A session on April 24 from 2-3 pm Central Time. Attendees can register here.

Progress towards a Thermostabilized, Single-Vial, COVID-19 Subunit Vaccine with a Nano-emulsion Adjuvant presented by Dr. Oreola Donini, Chief Scientific Officer, at the Annual Conference on Vaccinology Research, April 26-27, 2021. Attendees can register here.

Topical hypericin ointment photodynamic therapy is effective and safe in CTCL (FLASH study) presented by Dr. Ellen Kim, Lead FLASH Investigator, at the Society for Investigative Dermatology Virtual Meeting, May 3-8, 2021. Attendees can register here.

About HyBryte

HyBryte (SGX301) is a novel, first-in-class, photodynamic therapy utilizing safe, visible light for activation. The active ingredient in HyBryte is synthetic hypericin, a potent photosensitizer that is topically applied to skin lesions that is taken up by the malignant T-cells, and then activated by visible light 16 to 24 hours later. The use of visible light in the red-yellow spectrum has the advantage of penetrating more deeply into the skin (much more so than ultraviolet light) and therefore potentially treating deeper skin disease and thicker lesions. This treatment approach avoids the risk of secondary malignancies (including melanoma) inherent with the frequently employed DNA-damaging drugs and other phototherapy that are dependent on ultraviolet exposure. Combined with photoactivation, hypericin has demonstrated significant anti-proliferative effects on activated normal human lymphoid cells and inhibited growth of malignant T-cells isolated from CTCL patients. In a published Phase 2 clinical study in CTCL, patients experienced a statistically significant (p=0.04) improvement with topical hypericin treatment whereas the placebo was ineffective. HyBryte has received orphan drug and fast track designations from the FDA, as well as orphan designation from the European Medicines Agency (EMA).

The Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) trial enrolled a total of 169 patients (166 evaluable) with Stage IA, IB or IIA CTCL. The trial consisted of three treatment cycles. Treatments were administered twice weekly for the first 6 weeks and treatment response was determined at the end of the 8th week of each cycle. In the first double-blind treatment cycle, 116 patients received HyBryte treatment (0.25% synthetic hypericin) and 50 received placebo treatment of their index lesions. A total of 16% of the patients receiving HyBryte achieved at least a 50% reduction in their lesions (graded using a standard measurement of dermatologic lesions, the CAILS score) compared to only 4% of patients in the placebo group at 8 weeks (p=0.04) during the first treatment cycle (primary endpoint). HyBryte treatment in the first cycle was safe and well tolerated.

In the second open-label treatment cycle (Cycle 2), all patients received HyBryte treatment of their index lesions. Evaluation of 155 patients in this cycle (110 receiving 12 weeks of HyBryte treatment and 45 receiving 6 weeks of placebo treatment followed by 6 weeks of HyBryte treatment), demonstrated that the response rate among the 12-week treatment group was 40% (p<0.0001 vs the placebo treatment rate in Cycle 1). Comparison of the 12-week and 6-week treatment groups also revealed a statistically significant improvement (p<0.0001) between the two groups, indicating that continued treatment results in better outcomes. HyBryte continued to be safe and well tolerated. Additional analyses also indicated that HyBryte is equally effective in treating both plaque (response 42%, p<0.0001 relative to placebo treatment in Cycle 1) and patch (response 37%, p=0.0009 relative to placebo treatment in Cycle 1) lesions of CTCL, a particularly relevant finding given the historical difficulty in treating plaque lesions in particular.

The third (optional) treatment cycle (Cycle 3) was focused on safety and all patients could elect to receive HyBryte treatment of all their lesions. Of note, 66% of patients elected to continue with this optional compassionate use / safety cycle of the study. Of the subset of patients that received HyBryte throughout all 3 cycles of treatment, 49% of them demonstrated a treatment response (p<0.0001 vs patients receiving placebo in Cycle 1). Moreover, in a subset of patients evaluated in this cycle, it was demonstrated that HyBryte is not systemically available, consistent with the general safety of this topical product observed to date. At the end of Cycle 3, HyBryte continued to be well tolerated despite extended and increased use of the product to treat multiple lesions. Follow-up visits were completed in Q4 2020, and the clinical study report to support the NDA is in the process of being finalized.

Overall safety of HyBryte is a critical attribute of this treatment and was monitored throughout the three treatment cycles (Cycles 1, 2 and 3) and the 6-month follow-up period. HyBryte’s mechanism of action is not associated with DNA damage, making it a safer alternative than currently available therapies, all of which are associated with significant and sometimes fatal, side effects. Predominantly these include the risk of melanoma and other malignancies, as well as the risk of significant skin damage and premature skin aging. Currently available treatments are only approved in the context of previous treatment failure with other modalities and there is no approved front-line therapy available. Within this landscape, treatment of CTCL is strongly motivated by the safety risk of each product. HyBryte potentially represents the safest available efficacious treatment for CTCL. With no systemic absorption, a compound that is not mutagenic and a light source that is not carcinogenic, there is no evidence to date of any potential safety issues.

The Phase 3 CTCL clinical study was partially funded by the National Cancer Institute via a Phase II SBIR grant (#1R44CA210848-01A1) awarded to Soligenix, Inc.

About CiVax

CiVax is the Company’s heat stable subunit vaccine candidate for the prevention of COVID-19, the infection caused by SARS-CoV-2. Under the Company’s Public Health Solutions business segment, ongoing collaborations with Axel Lehrer, PhD of the Department of Tropical Medicine, Medical Microbiology and Pharmacology, JABSOM, UHM have demonstrated the feasibility of developing heat stable subunit filovirus vaccines, including hemorrhagic disease caused by Zaire ebolavirus, Sudan ebolavirus as well as Marburg marburgvirus, with both monovalent and bivalent vaccine combinations. Formulation conditions have been identified to enable heat stabilization of each antigen, alone or in combination, for at least 12 weeks at 40 degrees Celsius (104 degrees Fahrenheit). In March 2020, Soligenix and its collaborators expanded the technology platform to assess compatibility with vaccine candidates targeting SARS-CoV-2, the cause of COVID-19.

The vaccine platform includes three essential components:

a protein antigen, specifically a viral surface glycoprotein, which mediates entry and fusion of the virus with host cells and is manufactured with a proprietary insect cell expression system coupled with protein-specific affinity purification;
an adjuvant which has been shown to enhance both cell mediated and humoral immunity; and
a formulation which enables thermostabilization of the resulting mixture, avoiding the need for cold chain storage and shipping.
The resulting vaccine is broadly applicable, including to individuals often excluded from common viral vector vaccine approaches such as children, the elderly and the immunocompromised. The protection of elderly and immunocompromised populations are particularly important in the context of COVID-19. The ability to provide a thermostabilized, single vial vaccine, is particularly important in the context of rapid and broad vaccine distribution.

These same components are now being applied to coronavirus vaccine, using the well-defined surface glycoprotein, known as the Spike protein, as the antigen. Nonclinical work in mice with a prototype vaccine recently have been made available, demonstrating the ability of the CoVaccine adjuvant in combination with a prototype antigen, to:

stimulate immunity within 14 days after the first vaccination;
induce a balanced Th1 response, believed to be critical to inducing immunity without aggravating disease pathology;
induce a neutralizing antibody response; and
induce a cell mediated immune response.
CiVax development is being funded through an SBIR grant from NIAID (grant number 1 R44 AI157593-01).