On April 15, 2021 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that it has entered into a joint research collaboration with MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer (Press release, Alligator Bioscience, APR 15, 2021, View Source [SID1234578059]). The research collaboration will lead to the expansion of Alligator’s proprietary patient specific immunotherapy Neo-X-Prime by incorporating MacroGenics’ proprietary DART and TRIDENT multi-specific platforms against two undisclosed targets.

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!

Under the joint research collaboration agreement, which covers activities from candidate drug generation up until IND-enabling studies, each company will be responsible for its own costs. The parties may continue further development of the resulting bispecific molecule under a separate co-development collaboration and licensing agreement.

"We are truly excited to start this collaboration with MacroGenics, validating the Neo-X-Prime drug concept. The aim is to create a drug candidate that takes advantage of a unique mechanism of a patient’s own immune system to fight cancer. We look forward to working collaboratively to expand the Neo-X-Prime concept with MacroGenics’ antibodies, their proven DART technology, and extensive capabilities," says Malin Carlsson, interim CEO of Alligator Bioscience.

The Chairman of Alligator Bioscience, Peter Benson stated "MacroGenics is widely viewed as a leader in the antibody field as evidenced by their extensive pipeline of antibody-based molecules in clinical testing that are based on various platform technologies. Furthermore, MacroGenics’ capabilities are an excellent fit with Alligator’s strategy to develop next generation tumor specific immunotherapies to improve the lives of cancer patients."

Neo-X-Prime is a drug concept for more personalized immunotherapy, launched by Alligator in 2020. The concept builds on bispecific antibodies that physically link circulating tumor material to the immune system, to allow neoantigen-specific T cell priming with potential for superior anti-tumor efficacy.

MacroGenics’ DART and TRIDENT multi-specific platforms enable the creation of potential medicines comprised of a single molecule designed to simultaneously bind to two or more targets, each with antibody-like specificity, with the goal of creating a more significant biological effect.

On April 15, 2021 Clarity Pharmaceuticals, a clinical stage radiopharmaceutical company focused on the treatment of serious disease, reported that the first patient has been treated in the Phase II DISCO trial (Diagnostic Imaging Study of Copper-64 SARTATE Using PET on Patients With Known or Suspected Neuroendocrine Tumors) (Press release, Clarity Pharmaceuticals, APR 15, 2021, View Source [SID1234578042]).

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 DISCO trial (NCT04438304)1 is assessing the performance of 64Cu-SARTATE imaging agent in participants with known or suspected gastroenteropancreatic (GEP) NETs as a potential new way to help diagnose NETs. It is a Phase II study in 63 patients across 3 sites in Australia that compares the diagnostic performance of 64Cu-SARTATE at 4 and 20 hours to the current standard of care 68Ga-DOTATATE at 1 hour.

NETs, also known as well-differentiated neuroendocrine neoplasms or carcinoids, are a heterogeneous group of malignant transformations of cells of the diffuse neuroendocrine system. The most common site of primary NETs is the gastrointestinal tract (GI) (about 60% of all cases), followed by the bronchopulmonary tree (27%). Less frequent sites are the pancreas, biliary tract, liver, ovaries and testes.2 In 2020, the National Cancer Institute (NCI) estimated a prevalence close to 300,000 individuals who had a NET diagnosis and are currently alive in the U.S. Only 15% are survivors of 1 or less years from diagnosis.

A delay in diagnosis or misdiagnosis of NETs is common, such that most NET patients have metastatic disease by the time a diagnosis is confirmed.3 About 30-75% of NETs patients have distant metastases at the time of diagnosis according to the US and European cancer registries.

Clarity’s Executive Chairman, Dr Alan Taylor, commented: "There is a clear unmet need in the diagnosis of NETs with the frightening proportion of people currently being diagnosed when the cancer has already spread in their bodies, limiting treatment options and negatively affecting prognosis.

"Our 64Cu-SARTATE first-in-human diagnostic trial in NETs has demonstrated promising results in the safety and potential effectiveness of the product as a new way to detect neuroendocrine cancers (Hicks, R. et al. 2018)4. The study showed that the longer 12.7 hour half-life of Cu-64, combined with the stability of our proprietary SAR chelator which does not leak copper over time, proved to be advantageous in identifying additional tumour burden as it allows clinicians to have the flexibility to image patients at later time points than products based on Ga-68 or copper-based products that employ inferior chelators," said Dr Taylor.

The longer half-life of Cu-64 also enables product supply benefits. In the DISCO trial, clinical sites across Australia will be supplied 64Cu-SARTATE from a central radiopharmacy. In contrast, Ga-68 based products have to be synthesised on site and require the clinical sites to have local radiopharmacies.

"Our team is very excited to progress the development of 64Cu-SARTATE for NET patients to expand the patient population for SARTATE from neuroblastoma in children. We are also looking forward to capitalising on the many benefits of the "perfect pairing" of Cu-64 and Cu-67 for imaging, therapy, manufacture and logistics in the development of all of our pipeline products with the ultimate goal of improving treatment outcomes for children and adults with cancer," commented Dr Taylor.

Reference List
A Diagnostic Imaging Study of 64Cu-SARTATE Using PET on Patients With Known or Suspected Neuroendocrine Tumors, <View Source>
Modlin, E. et al. 2010, "Gastrointestinal neuroendocrine (carcinoid) tumours: current diagnosis and management", The Medical Journal of Australia, <View Source>
Basuroy, R. et al. 2018, "Delays and routes to diagnosis of neuroendocrine tumours", BMC Cancer, <View Source>
Hicks, R. et al. 2018, "First-in-human trial of 64Cu-SARTATE PET imaging of patients with neuroendocrine tumours demonstrates high tumor uptake and retention, potentially allowing prospective dosimetry for peptide receptor radionuclide therapy", The Journal of Nuclear Medicine, <View Source>

On April 14, 2021 Samsung Biologics reported on the 17th 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 [SID1234633685]).

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!

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 14, 2021 Celularity Inc. ("Celularity"), a clinical-stage biotechnology company, leading the next evolution in cellular medicine with the development of off-the-shelf allogeneic therapies derived from the postpartum human placenta, reported the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to the company’s non-genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, CYNK-001, for the treatment of patients with malignant gliomas (Press release, Celularity, APR 14, 2021, View Source [SID1234578060]). CYNK-001 is currently being investigated in a phase 1 clinical trial (NCT04489420) for the treatment of patients with glioblastoma multiforme (GBM), an indication within the scope of this orphan designation.

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!

"We are very pleased the FDA has granted Orphan Designation in malignant gliomas to continue to develop off-the-shelf therapies for serious unmet clinical needs," said Robert J. Hariri, M.D., Ph.D., founder, Chairperson and Chief Executive Officer of Celularity. "Building on the FDA’s recent decision to grant Fast Track status to CYNK-001, we view the Orphan Drug Designation as yet another milestone on our journey to deliver patients a potentially novel treatment. To date, we have observed the potential of CYNK-001 in multiple preclinical models as well as early evidence of activity in the clinic and believe this approach may shift the paradigm in augmenting the body’s natural immune response to diseases such as glioblastoma, other cancer indications and infectious diseases. We are very excited to continue working with the FDA on the development of this exciting therapy."

About Orphan Drug Designation

The Orphan Drug Act (ODA) encourages biotechnology and pharmaceutical companies to develop drugs for conditions which affect fewer than 200,000 people in the United States by providing economic incentives. To qualify for orphan designation, both the drug and the condition must meet criteria specified in the ODA and FDA’s implementing regulations 21 CFR Part 316. Orphan designation qualifies the drug sponsor for development incentives including tax credits for qualified expenses, reduction in the FDA user fee, and seven years of exclusivity for a drug that obtains approval.

About Malignant Gliomas

Glioma is a type of tumor that occurs in the brain and spinal cord. Malignant gliomas consist of glioblastoma multiforme (GBM), anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, anaplastic ependymoma, and anaplastic ganglioglioma. Malignant gliomas are associated with high morbidity and mortality. GBM accounts for the majority of malignant gliomas. Currently there are no effective long-term treatments for the disease. Patients with GBM usually survive less than 15 months following diagnosis. In most patients, the rapidly growing malignant tumor tends to recur within 6-8 months following treatment. Patients with recurrent GBM have even poorer prognosis. Therefore, malignant gliomas, such as GBM, are serious diseases with high unmet medical needs.

About CYNK-001

Celularity’s lead therapeutic program based on its placental-derived unmodified NK cell type is CYNK-001, an allogeneic unmodified NK cell being developed as a treatment for hematologic malignancies, solid tumors, and infectious diseases.

On April 14, 2021 GeneLeap Bio., a subsidiary of Luye Life Sciences specializing in the development of nucleic acid therapeutics, reported that an ePoster entitled ‘Hydrogel encapsulated TLR9 agonists show sustained tumor growth inhibition and prolong survival of CT26 tumor-bearing mice’ at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting (Press release, GeneLeap Bio, APR 14, 2021, View Source [SID1234578058]). The preclinical study shows that compared with using TLR9 agonist on its own, a hydrogel encapsulated TLR9 agonist, independently developed by GeneLeap Biotech, can significantly improve antitumor performance, while demonstrating tumor growth inhibitory effects similar to that of TLR9 agonist without hydrogel encapsulation.

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!

AACR Annual Meeting is one of the world’s biggest and most eminent conferences related to cancer research, covering the latest discoveries and drug developments across the spectrum of cancers and highlighting the work of the best minds in research and medicine from institutions all over the world. The meeting was held virtually this year, from April 10 to 15 and May 17 to 21.

TLR9 is one of the most promising targets in current cancer immunotherapies, whose agonist has emerged as a potential monotherapy or in combination with other anticancer therapies. As an innate immune stimulator, TLR9 agonist can be combined with checkpoint inhibitors to increase its anti-tumor effects. By activating the innate immune system, it provides increased immunological impetus against checkpoint inhibitor resistant and refractor tumors.

However, there are certain drawbacks in the clinical application of TLR9 agonist, such as increased toxicity seen with systemic administration. Local injection of the TLR9 agonist is well-tolerated but the drug can degrade in the local tissues or dissipate from the site of action rapidly, resulting in reduced efficacy. Thus, in such cases a weekly or biweekly dosing of TLR9 agonist is usually required to maintain the anti-tumor efficacy.

To address this medical need, GeneLeap Biotech has made a breakthrough by encapsulating TLR9 agonists in injectable hydrogels containing poloxamer for a slow and sustained release of TLR9 agonist over a period of time. GeneLeap’s researchers have conducted preclinical studies in a mouse tumor model to examine whether a single dose of Hydrogel encapsulated TLR9 agonist can be effective over a longer period in immune activation without toxicity.

The current preclinical study showed that a single administration of hydrogel encapsulated TLR9 agonist demonstrates tumor growth inhibition and non-toxicity similar to that of a multiple dose of TLR9 agonist without hydrogel encapsulation. This indicates that for those patients who are resistant or refractory to checkpoint inhibitors, hydrogel encapsulated TLR9 agonist could enhance the immune response to checkpoint inhibitors for a longer time. "Based on the positive preclinical data obtained in a mouse tumor model, we believe this novel formulation – hydrogel encapsulation – will ease frequency of dosing schedules of TLR9 agonists in clinic," said Dr. Jason Zhang, CSO of GeneLeap Biotech.

This preclinical study is also of pioneering significance in exploring further applications of hydrogel formulations. "To our knowledge, this is the first study using hydrogel encapsulation to improve the frequency of dosing of TLR9 agonists in cancer patients," said CEO of GeneLeap Biotech, Dr. Sean Fu. "It helps us enhance understanding of hydrogel formulations and has laid a good foundation for more in-depth clinical research in the area of therapeutic modalities including mRNA and oligonucleotides. As a pharmaceutical biotech focusing on frontier science, GeneLeap Biotech is committed to promoting pioneering science, developing nucleic-acid drugs for tumors and severe infectious diseases, and providing patients with innovative treatments to meet their health needs."