On June 22, 2022 Aura Biosciences Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported results from a retrospective, matched case control study (Press release, Aura Biosciences, JUN 22, 2022, View Source [SID1234616167]). This retrospective analysis assessed the visual acuity of patients following treatment with plaque radiotherapy compared with prospective data on visual acuity in subjects with early-stage choroidal melanoma treated with belzupacap sarotalocan by intravitreal administration in the Phase 1b/2 trial (NCT03052127).

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"These results point to the high unmet medical need for a first line vision preserving therapy for the treatment of early-stage choroidal melanoma given the high levels of irreversible visual acuity loss with the current standard of care with radiotherapy," said Carol Shields, MD, Chief of the Ocular Oncology Service at Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University. "Being able to treat the disease early, avoid radiotherapy and spare long-term vision loss in many patients, as well as potentially reducing the risk of metastatic disease, could represent a paradigm shift in our approach to the treatment of choroidal melanoma. This would be a significant improvement in the quality of life for patients with this life-threatening rare disease."

Results from the Retrospective Study

Study Design

This retrospective, matched case control study compared visual acuity outcomes for 43 patients from Aura’s Phase 1b/2 trial evaluating intravitreal administration of belzupacap sarotalocan in patients with early-stage choroidal melanoma (AU-011-101, NCT03052127) to 150 patients from the subject database of a previously completed and published study where patients with small choroidal melanoma had been treated with plaque radiotherapy (Shields, et al. "Visual Outcome and Millimeter Incremental Risk of Metastasis in 1780 Patients With Small Choroidal Melanoma Managed by Plaque Radiotherapy." JAMA Ophthalmology. September 27, 2018). Both cohorts of patients were at high risk for vision loss due to having the tumor edge within 3.0 mm of the fovea. The patients were matched for tumor height, tumor diameter, distance from the fovea and baseline visual acuity, which are among the core factors that impact visual acuity after treatment.

Key Findings:

The vision results of patients with early-stage choroidal melanoma treated with radiotherapy showed the long term, progressive and irreversible loss of visual acuity in patients where tumors were close to the fovea.

The loss of vision in radiotherapy patients was ≥3 lines in a majority of patients as early as 2 years and ≥6 lines as early as 3 years.

We believe the comparison of the belzupacap sarotalocan and radiotherapy results supports the potential benefit of a targeted treatment achieving a statistically significant difference in visual acuity preservation as soon as two years including for both logMAR (Logarithm of the Minimum Angle of Resolution) vision (p = 0.0094) and change in logMAR vision (p = 0.0323).

We believe the progressive loss of visual acuity with radiotherapy observed in this retrospective study underscores the urgent need for a vision preserving targeted therapy.

The findings of this retrospective study were consistent with published clinical data supporting the irreversible loss of visual acuity after treatment with radiotherapy.

"We are committed to developing the first potential targeted therapy for patients with early-stage choroidal melanoma. We believe the visual acuity results of the retrospective matched case control study are exciting because they support the high unmet medical need for a long-term vision preserving therapy," said Dr. Cadmus Rich, Chief Medical Officer and Head of R&D of Aura Biosciences. "Belzupacap sarotalocan is currently being evaluated in a Phase 2 dose escalation clinical trial (AU-011-202, NCT04417530) using suprachoroidal administration in patients with early-stage choroidal melanoma. We remain on track to initiate our pivotal trial by the end of 2022."

Study Limitations include the retrospective nature and utilizing a matched case control design. The mean follow-up for patients treated with belzupacap sarotalocan in this initial analysis was 15.6 months. Due to the retrospective nature of this analysis, it is hypothesis-generating; no formal conclusions can be drawn. Aura has also initiated a prospective matched case control study to further evaluate the long-term visual acuity results of belzupacap sarotalocan from the Phase 2 trial AU-011-202 using suprachoroidal administration versus radiotherapy.

On June 22, 2022 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that the U.S. Food and Drug Administration ("FDA") has granted Orphan Drug Designation to MB-106, Mustang’s CD20-targeted, autologous CAR T cell therapy for the treatment of Waldenstrom macroglobulinemia ("WM" or "Waldenstrom"), a rare type of B-cell non-Hodgkin lymphoma ("B-NHL") (Press release, Mustang Bio, JUN 22, 2022, View Source [SID1234616183]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Center ("Fred Hutch") to treat patients with relapsed or refractory B-NHLs and chronic lymphocytic leukemia ("CLL").

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The FDA grants Orphan Drug Designation to drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. Orphan Drug Designation provides certain incentives, such as tax credits toward the cost of clinical trials upon approval and prescription drug user fee waivers. If a product receives Orphan Drug Status from the FDA, that product is entitled to seven years of market exclusivity for the disease in which it has Orphan Drug designation, which is independent from intellectual property protection.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are very pleased to receive Orphan Drug Designation from the FDA, as it is an important regulatory milestone for Mustang’s MB-106 program for the treatment of Waldenstrom macroglobulinemia, a rare B-NHL with a significant unmet medical need. We look forward to dosing the first patient in our multicenter Phase 1/2 clinical trial evaluating the safety and efficacy of MB-106 for relapsed or refractory B-NHL and CLL under Mustang’s IND shortly. In the Phase 1 portion of this trial, MB-106 dose escalation will proceed in three separate arms, and Waldenstrom patients will be included in the indolent lymphoma arm in parallel with accrual of patients to the aggressive lymphoma and CLL arms."

MB-106 data presented earlier this month at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress continue to demonstrate high efficacy and a very favorable safety profile across all five dose levels. The overall response ("ORR") was 96% across all dose levels and all indications (n=26). In particular, the 100% complete response rates by PET scan of patients with WM (n=2) as well as of patients with B-NHL previously treated with CD19-directed CAR T cell therapy (n=2) underscore the potential for MB-106 to treat these patient populations with high unmet needs. Durable responses were observed in a wide range of hematologic malignancies including follicular lymphoma, CLL, diffuse large B-cell lymphoma and WM. The possible outpatient administration of this therapy makes it potentially even more compelling. Currently no CAR T therapy is specifically approved for WM.

Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

About Waldenstrom Macroglobulinemia
Waldenstrom macroglobulinemia ("WM"), also known as lymphoplasmacytic lymphoma, is a rare type of non-Hodgkin lymphoma ("NHL"), a malignant disorder of the bone marrow and lymphatic tissues. The proliferation of cancer cells can crowd out normal cells in these tissues, leading to low levels of red blood cells, white blood cells, and platelets which, in turn, causes fatigue, shortness of breath, infections, bruising, and bleeding. In addition, the cancer cells make large amounts of the large antibody protein immunoglobulin M, or IgM, which cause the blood to become thick. This hyperviscosity of the blood affects its flow through the smaller blood vessels, leading to some of the other manifestations of the disease, such as visual and neurological symptoms. WM is a rare disorder with an incidence of approximately 3 per million people per year, and 1,400 new cases are diagnosed in the U.S. each year. The median age at diagnosis is 70 years.

About MB-106 (CD20-targeted autologous CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and was exclusively licensed to Mustang in 2017. The lentiviral vector drug substance used to transduce patients’ cells to create the MB-106 drug product produced at Fred Hutch has been optimized as a third-generation CAR derived from a fully human antibody. MB-106 is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. The same lentiviral vector drug substance produced at Fred Hutch will be used to transduce patients’ cells to create the MB-106 drug product produced at Mustang Bio’s Worcester, MA, cell processing facility for administration in the multicenter Phase 1/2 clinical trial that is now open to enrollment under Mustang Bio’s IND. It should be noted that Mustang Bio has introduced minor improvements to its cell processing to facilitate eventual commercial launch of the product. In addition, prior to commercial launch, Mustang Bio will replace the Fred Hutch lentiviral vector drug substance with vector produced at a commercial manufacturer. Additional information on these trials can be found at View Source using the identifier NCT05360238 for the Mustang multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch.

On June 22, 2022 AVEO Oncology (Nasdaq: AVEO), a commercial stage, oncology-focused biopharmaceutical company, reported that it has entered into a clinical trial collaboration and supply agreement in North America with Eli Lilly and Company (Lilly) to evaluate ficlatuzumab in combination with ERBITUX (cetuximab), an anti-EGFR antibody, in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) (Press release, AVEO, JUN 22, 2022, View Source [SID1234616168]). Ficlatuzumab is AVEO’s investigational potent humanized immunoglobulin G1 monoclonal antibody that targets hepatocyte growth factor.

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"This clinical trial collaboration and supply agreement with Lilly follows a similar engagement we entered into with Merck KGaA, Darmstadt, Germany earlier this year, both of which we believe serve as validation for our ficlatuzumab clinical development plan. We expect these collaborations will play an important role in the advancement of the combination of ficlatuzumab and cetuximab," said Michael Bailey, president and chief executive officer of AVEO. "We reported positive Phase 2 clinical data last year that show ficlatuzumab in combination with cetuximab has the potential to play a meaningful role in the treatment of patients with human papillomavirus (HPV) negative R/M HNSCC, which is associated with particularly poor outcomes. We continue to be in discussions with regulators on the final design of a potential pivotal study for this combination therapy, which we expect to commence in the first half of 2023."

Under the terms of the agreement, Lilly will provide cetuximab clinical drug supply in the U.S. and Canada for AVEO’s potential registrational study, which will assess ficlatuzumab with cetuximab in HPV negative R/M HNSCC. AVEO will serve as the study sponsor and will be responsible for trial execution.

In June 2021, AVEO announced positive results from a randomized Phase 2 study of ficlatuzumab alone or in combination with cetuximab in patients with pan-refractory metastatic HNSCC. Of note, patients with HPV negative disease, a subgroup normally associated with poorer outcomes, who received the ficlatuzumab and cetuximab combination demonstrated both a superior overall response rate, including two patients with complete responses, and median progression free survival superior to historical data for current standards of care. In September 2021, the FDA awarded Fast Track designation for the combination of ficlatuzumab and cetuximab in HPV negative relapsed/recurrent HNSCC. A copy of the presentation is available at www.aveooncology.com.

AVEO recently commenced manufacturing of ficlatuzumab clinical supply in the second quarter of 2022, with the potential registrational study expected to be initiated in the first half of 2023. AVEO expects to continue to discuss potential ficlatuzumab pivotal study designs with the FDA and to continue ongoing partnership dialogues.

About Ficlatuzumab

Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) immunoglobulin G1 (IgG1) inhibitory antibody that binds to the HGF ligand with high affinity and specificity. HGF is the natural ligand of c-Met and blocking HGF inhibits signaling through the HGF/c-Met signaling pathway. Ficlatuzumab is currently being evaluated in squamous cell carcinoma of the head and neck (HNSCC) and pancreatic cancer. The U.S. Food and Drug Administration designated as a Fast Track development program the investigation of ficlatuzumab and ERBITUX (cetuximab) for relapsed/recurrent HNSCC in September 2021.

On June 22, 2022 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that the results from a small trial of just 18 rectal cancer patients in complete remission using an immunotherapy called dostarlimab are "impressive," whilst acknowledging there’s more work to be done (Press release, Propanc, JUN 22, 2022, View Source [SID1234616184]). Chief Scientific Officer and Co-Founder, Dr Julian Kenyon MD, MB, ChB, believes that the field’s biggest challenge remains that immunotherapies work inconsistently across cancers. Oncologists estimate a response rate of 20% across cancer types, according to the Wall Street Journal ("WSJ"). The drugs can wipe out cancers from some people, but fail to work for others. It is also uncertain whether the cancer may eventually return once a patient is in remission, even after a prolonged period of time.

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Immunotherapies like dostarlimab, known as a checkpoint inhibitor, seek to inhibit key regulators of the immune system that when stimulated, reduces the body’s immune response to fight cancer. Given that immunotherapies target specific gene sequences, it often means they can encounter resistance, due to mutations that occur and genetic variation even within the primary tumor of a patient. As a result, Dr Cercek, from Memorial Sloan Kettering, who conducted the study for dostarlimab, estimates only 10% of rectal cancer patients and about 4% of all cancers will respond to treatment, according to the WSJ.

"For many cancers, multiple factors can drive growth, making it hard to effectively match one biomarker, or a particular gene sequence, to a single drug. On the other hand, a therapeutic approach like our lead product candidate, PRP, which alters the characteristics of the cancer cell, by enforcing it to express proteins it normally wouldn’t, means the treatment is less likely to encounter resistance through mutations, which is what we have observed in the lab as well as in clinical practice," said Dr Julian Kenyon.

In addition to specifically selecting the 18 rectal cancer patients according to their genetic biomarker, the trial included patients that were pre-metastatic, where tumors were locally advanced in one area, but not spread to other organs. This means patients identified with metastatic cancer were excluded from the trial. Therefore, the treatment and prevention of metastatic cancer, the main cause of patient death for sufferers, still remains the unsolved, final frontier. Cancer stem cells, which are the cells responsible for spreading to other parts of the body, remains a key focus for Dr Kenyon.

Dr Kenyon said, "PRP is a proenzyme treatment that targets and eradicates cancer stem cells by altering multiple pathways of a cancerous cell rather than a single genetic sequence. We’ve observed that once they are treated with PRP, the effects are irreversible and are more easily recognizable by the immune system, therefore potentially improving the response rates of standard approaches like immunotherapy, to overcome advanced cancers. We look forward to testing the utility of PRP with these approaches as we further advance into the clinic."

PRP is a mixture of two proenzymes, trypsinogen and chymotrypsinogen from bovine pancreas administered by intravenous injection. A synergistic ratio of 1:6 inhibits growth of most tumor cells. Examples include kidney, ovarian, breast, brain, prostate, colorectal, lung, liver, uterine and skin cancers.

On June 22, 2022 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported the signing of a definitive agreement for the sale of revenues from U.S. and European royalty and milestone interests in Klisyri (tirbanibulin) to Sagard Healthcare Partners and funds managed by Oaktree Capital Management, L.P. ("Oaktree") for $85 million (Press release, Athenex, JUN 22, 2022, View Source [SID1234616235]). Approximately $80 million of the proceeds from the transaction will be used toward partially paying down existing debt and operating the business, with $5 million to be placed into escrow and paid to Athenex upon the satisfaction of certain conditions. The transaction is subject to customary closing conditions.

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"We are executing on our new strategy and will continue to deliver on the objectives that we laid out to extend our cash runway by over 18 months. We are pleased to enter into this agreement, as we believe it generates meaningful benefits for our stockholders as we continue to pay down debt and extend our cash runway," said Dr. Johnson Lau, Chief Executive Officer of Athenex. "The sale of the revenues from the U.S. and European royalty and milestone interests in Klisyri represents another step in continuing to monetize non-core assets to focus on developing our potential best-in-class NKT cell platform."

Ladenburg Thalmann & Co. Inc. and Royalty/Revenue Interest Capital Advisors LLC served as financial advisors to Athenex and Cooley LLP served as legal counsel to Athenex. Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. served as legal counsel to Sagard Holdings and Oaktree.