On June 17, 2022 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that the United States Food and Drug Administration (FDA) has awarded Orphan Drug Designation (ODD) to Kazia’s paxalisib for the treatment of atypical rhabdoid / teratoid tumors (AT/RT), a rare and highly-aggressive childhood brain cancer (Press release, Kazia Therapeutics, JUN 17, 2022, View Source [SID1234616084]).

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Key Points

Orphan Drug Designation (ODD) is a special status accorded to drugs which are considered promising potential treatments for rare (‘orphan’) diseases, generally defined as those which affect less than 200,000 cases per annum in the United States.

ODD can provide drug developers with up to seven years of Orphan Drug Exclusivity (ODE), during which competitors may not rely on Kazia’s data to develop generic versions of paxalisib, effectively extending the effective life of a commercial product. It also provides opportunities for grant funding and protocol assistance, and tax credits.

FDA will waive fees relating to a future regulatory filing in AT/RT, potentially saving more than US$3 million if Kazia seeks approval in this indication.

Paxalisib has previously been granted ODD in malignant glioma, a category of brain cancer that includes both glioblastoma, an adult brain cancer which is the lead indication for the drug, and diffuse intrinsic pontine glioma (DIPG), a rare childhood brain cancer which is currently the subject of a phase II study led by the Pacific Pediatric Neuro-Oncology Consortium.

Kazia CEO, Dr James Garner, commented, "childhood brain cancer has emerged as an important area of focus for the paxalisib program. We have been working for some years with several world-leading researchers in DIPG, one of the most aggressive childhood cancers. Recent data presented at the AACR (Free AACR Whitepaper) conference by Dr Jeffery Rubens and colleagues from Johns Hopkins Medical School has shown the potential of the drug to also add benefit in AT/RT, another form of childhood brain cancer that is very poorly served by existing treatments. This represents an important new opportunity for paxalisib, and one that we continue to explore enthusiastically with our collaborators and advisors."

Board of Directors

Mr Iain Ross Chairman, Non-Executive Director

Mr Bryce Carmine Non-Executive Director

Mr Steven Coffey Non-Executive Director

Dr James Garner Chief Executive Officer, Managing Director

Three International Towers, Level 24, 300 Barangaroo Avenue, Sydney NSW 2000

Orphan Drug Designation

ODD exists to recognise and encourage the development of a drug for a rare disease, which may affect adults or children. ODD provides an additional period of 7.5 years data exclusivity (for a paediatric disease), which allows companies to better defend their products against competition. It also results in a waiver by FDA of fees for a marketing application, under the Prescription Drug User Fees Act (PDUFA fees), which are over US$ 3 million in FY2022. In addition, drugs with ODD may be eligible for orphan grants by FDA.

Kazia previously received ODD for paxalisib in glioblastoma in February 2018, and for malignant glioma in August 2020.

Next Steps

A phase II clinical trial of multiple drug therapies, including paxalisib, is ongoing, under the sponsorship of the Pacific Pediatric Neuro-Oncology Consortium (PNOC) (NCT05009992). This study combines several investigational drugs in the treatment of patients with diffuse midline gliomas (DMGs), a category which includes DIPG. Initial data from this study is anticipated in CY2023.

A phase I study of paxalisib in DIPG, led by St Jude Children’s Research Hospital in Memphis, TN (NCT03696355), is nearing completion, and final data is expected to be submitted for publication by the end of CY2022.

Kazia Therapeutics will participate in a webinar to discuss the company’s activities in childhood brain cancer on Wednesday 22nd June 2022. Registration details are available via the company website.

On June 17, 2022 Brooklyn ImmunoTherapeutics, Inc. (Nasdaq:BTX) ("Brooklyn" or the "Company"), a biopharmaceutical company focused on developing advanced therapies using state-of-the-art mRNA cell engineering technology, reported that on June 17, 2022, it received a notice (the "Notice") from the Nasdaq Stock Market LLC ("Nasdaq"), stating that the Company is not in compliance with the minimum bid price requirement ("Minimum Bid Requirement") of US$1.00 per share under the Nasdaq Listing Rule 5450(a)(1) based upon the closing bid price of the Company’s common stock for the 30 consecutive business days prior to the date of the Notice (Press release, Brooklyn ImmunoTherapeutics, JUN 17, 2022, View Source [SID1234616085]). The Notice has no immediate effect on the listing or trading of the Company’s common stock on Nasdaq.

Under Nasdaq Listing Rule 5810(c)(3)(A), the Company has 180 calendar days from the date of the Notice, or December 14, 2022, to regain compliance with the Minimum Bid Requirement, during which time the Company’s common stock will continue to trade on Nasdaq. If at any time before December 14, 2022, the bid price of the common shares closes at or above US$1.00 per share for a minimum of 10 consecutive business days, the Company will regain compliance with the Minimum Bid Requirement. If the Company does not regain compliance with the Minimum Bid Requirement by December 14, 2022, the Company may be eligible, upon satisfaction of certain Nasdaq listing requirements, for an additional period of 180 calendar days to regain compliance or its common stock may be subject to delisting from Nasdaq.

The Company will closely monitor the closing bid price of its common stock and is considering its options to regain compliance with the Minimum Bid Requirement under the Nasdaq Listing Rules.

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On June 17, 2022 VBI Vaccines and Hepion Pharmaceuticals reported that it received Orphan Drug Designations from the U.S. Food and Drug Administration Friday for their experimental cancer drugs (Press release, Hepion Pharmaceuticals, JUN 17, 2022, View Source [SID1234616086]).

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Orphan Drug Designations are granted for drugs that show promise for treatment, prevention or diagnosis of orphan diseases, which in the U.S. is defined as affecting fewer than 200,000 people. It comes with certain incentives, including tax credits for qualified clinical trials, user fees exemption and potential seven years of market exclusivity after approval.

Based in Cambridge, MA, VBI received its designation for a bivalent cytomegalovirus gB/pp65 enveloped virus-like particles (VLPs) designed to treat glioblastoma, a type of brain cancer. The company focuses on developing VLPs, leveraging a proprietary enveloped VLP (eVLP) platform technology. These are so-called cancer vaccines that act by mimicking viruses with the intention of stimulating the human immune system.

Earlier this month, the company presented new tumor response and overall survival (OS) data from the ongoing Phase IIa trial of VBI-1901 in recurrent glioblastoma. It was included in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

David E. Anderson, Ph.D., chief scientific officer of VBI, said at the time, "We continue to be motivated by the data seen in this Phase IIa study of VBI-1901 as we endeavor to provide new treatment options to patients with very few available to them. Considering the high mortality rate among GBM patients, particularly in the recurrent setting, median overall survival of approximately 13-15 months seen in our two study arms suggests an additional survival benefit of nearly six months in comparison with historical control data in the recurrent population after treatment with a monotherapy."

He added, "Moreover, the correlation of tumor responses and clinical response benefit observed in tandem is very encouraging. We remain in close discussion with our study investigators and scientific advisors as we move toward the next stages of development in both the recurrent and frontline GBM settings, and look forward to advancing this development program as diligently as possible."

Hepion received the designation for rencofilstat for hepatocellular carcinoma. Rencofilstat is the company’s lead oral drug candidate for nonalcoholic steatohepatitis (NASH) and viral hepatitis-induced liver disease.

The drug binds to Cyclophilin A, which blocks it from binding to specific inflammatory cell receptors. This decreases the infiltration of the inflammatory cells into the tissue and lessens harmful inflammatory responses that can cause damage to the liver.

It also blocks the actions of Cycophilin B, which regulates collagen production in stellate cells, causing fibrosis (scarring) in the liver. And it binds to Cyclophilin D, preventing or reversing the formation of pores in the mitochondrial membrane that causes the mitochondria to rupture. This allows the mitochondria to resume normal energy production and helps liver cells survive.

In January, Hepion, headquartered in Edison, NJ, announced the results of a nonclinical research study of rencofilstat that decreased liver tumor growth and extended mouse survival when combined with an anti-PD-1 antibody, or immune checkpoint inhibitor. The effects were seen in fatty livers, which may be associated with less ant-PD-1 efficacy in hepatocellular carcinoma (HCC). This suggests that the drug may improve the treatment potential of anti-PD-1 treatment in human liver cancer. Examples of anti-PD-1 drugs include Merck’s Keytruda (pembrolizumab) and Bristol Myers Squibb’s Opdivo (nivolumab).

At the time, Daren Ure, Ph.D., Hepion’s chief scientific officer, noted, "Anti-PD-1 therapies that stimulate immune cell attack on cancer cells are approved and effective in many types of cancer, but they have had limited success in HCC clinical trials. The lack of clinical outcomes success may be partly due to the occurrence of HCC in individuals that also have non-alcoholic fatty liver disease (NAFLD) or the more advanced form of the disease, NASH."

He added, "NAFLD and NASH are both highly prevalent across the globe, and recent reports indicate that a fatty liver environment blocks the efficacy of anti-PD-1 drugs, and perhaps other checkpoint inhibitors. In addition, as successful treatments for viral hepatitis have been implemented, NASH has been quickly becoming the leading cause of HCC."

On June 17, 2022 Kineta, Inc. ("Kineta" or the "Company"), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology, reported that it presented the Phase 1/2 clinical trial design and new preclinical data supporting KVA12.1 as a potential treatment for cancer patients with advanced solid tumors at the Tumor Myeloid-Directed Therapies Summit held on June 14-16 in Boston, MA (Press release, Kineta, JUN 17, 2022, View Source;utm_medium=rss&utm_campaign=kineta-presents-new-preclinical-data-and-phase-1-2-clinical-trial-design-of-kva12-1-at-the-tumor-myeloid-directed-therapies-summit [SID1234616067]).

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Shaarwari Sridhar, Scientist at Kineta, presented a poster outlining the first-in-human clinical trial design and study objectives evaluating KVA12.1 as a monotherapy and in combination with an anti-PD1 immunotherapy. New preclinical and toxicology data supporting advancing KVA12.1 into clinical development were also presented. KVA12.1 is a potential best-in-class VISTA blocking immunotherapy that was discovered through the Company’s proprietary immuno-oncology PiiONEER platform. The Phase 1/2 study will be a multicenter, open label, dose escalation and dose expansion study of intravenous infusion of KVA12.1 as a monotherapy and in combination with a fixed dose of an anti-PD1 antibody in patients with advanced solid tumors. Kineta plans to initiate the Phase 1/2 clinical study in Q4 2022.

"We are very encouraged by the preclinical data and are excited for KVA12.1 to enter the clinic later this year," said Thierry Guillaudeux, PhD, EVP Research and Development at Kineta. "KVA12.1 was developed through Kineta’s PiiONEER platform as an engineered IgG1 monoclonal antibody that binds to a unique epitope at physiologic and acidic Ph levels. It is highly differentiated as it has demonstrated efficacy as a single agent and in combination with PD-1 in multiple tumor models with no CRS-associated cytokine secretion seen in preclinical tox studies."

Phase 1/2 clinical study objectives detailed in the poster presentation include:

Clinical
Safety measurements and DLTs as single agent and in combination with anti-PD1
Overall Response Rate and durability of response using RECISTv1.1
Determined MTD and R2PD
Pharmacologic and Biomarker
PK
Receptor Occupancy
Cytokine and Chemokine profiles in plasma samples
Flow Cytometry for PD marker on Immune cells
Tumor biopsies : multiparameter analysis to evaluate tumor cells as well as Immune infiltrating cells. Characterized expression of immune checkpoint and exhausted markers.
Presentation Details:

Title: KVA12.1 a novel fully human anti-VISTA antibody to treat cancer patients with advanced solid tumors
Date Presented: June 15-16, 2022
Presenter: Shaarwari Sridhar

For further details, please view the poster presentation on Kineta’s website here.

On June 17, 2022 Xspray Pharma (Nasdaq Stockholm: Xspray) reported that the US Food and Drug Administration (FDA) has granted Dasynoc Orphan Drug Designation (ODD) in the US for the treatment of chronic myeloid leukemia (CML) (Press release, Xspray, JUN 17, 2022, View Source [SID1234649576]).

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The FDA decision to grant the designation is based on the plausible hypothesis that Dasynoc may be clinically superior to the same drug(s) already approved for the same indication because Xspray Pharmas product candidate may provide a major contribution to patient care due to the gastric pH-resistant qualities of its formulation and in the context of significant concomitant use of acid reducing agents in the CML population.

"We are very pleased that our product candidate Dasynoc has been granted this orphan drug designation. This is our second product candidate to be granted this designation and it confirms both our technology and the unmet medical need that Xspray Pharma can address. This strengthens us in our goal to work with improved oncology pharmaceuticals and to provide patients a better quality of life", said Per Andersson, CEO of Xspray Pharma.

Dasynoc is Xspray Pharmas first product candidate and is currently under FDA review for approval. The FDA grants ODD status to medicines and potential new medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US.

Chronic myeloid leukemia – CML
CML is a type of blood cancer where the body produces malignant white blood cells. Almost all patients with CML have an abnormality known as the "Philadelphia chromosome," which produces a protein called BCR-ABL. This protein aids the proliferation of malignant white blood cells in affected patients. About 15% of all leukemia is CML. In 2020 it was projected that 8,450 people in the US would be diagnosed with CML and in 2017, there were an estimated 58,000 people living with the disease in the US.