Propanc Biopharma’s CEO Believes Lead Asset Could Unlock Value as PRP Advances to Phase I, First-In-Human Study in Advanced Cancer Patients

On July 12, 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 CEO and Co-Founder Mr. James Nathanielsz, BAS, MEI, believes the Company’s lead asset could unlock value as PRP advances to a Phase I, First-In-Human study in advanced cancer patients (Press release, Propanc, JUL 12, 2022, View Source [SID1234616618]). As a less toxic therapy compared to standard treatments with a unique approach for the treatment and prevention of metastatic cancer, PRP has the potential to be a welcome addition to the treatment process that is complementary to existing therapies. Notwithstanding recent advances in the oncology sector, metastasis from solid tumors remains the unsolved final frontier and is the biggest killer of cancer sufferers.

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Consequently, despite the relatively early stage of development of PRP, Mr. Nathanielsz comments that the clinical history of PRP in the treatment of cancer, as well as the positive results achieved in a physician sponsored investigator study of 46 late-stage advanced cancer patients suffering from a range of malignancies, conducted by Chief Scientific Officer and Co-Founder, Dr. Julian Kenyon, MD, MB, ChB, "Substantially alters the risk profile for success," compared to new and untried technologies at a similar stage of development. This has been substantiated by a third-party valuation undertaken by a North American investment bank, coordinated by the Company, which valued Propanc’s intellectual property (IP) assets at $26 million, despite a relatively early stage of development, based on the Company’s initial target patient populations, including pancreatic, ovarian, prostate and colorectal cancers.

To date, the Company has completed pivotal safety toxicology studies, as well as undertaking significant process development and purification processes for the active pharmaceutical ingredients in the PRP formulation, trypsinogen and chymotrypsinogen. As the Company completed these pivotal activities to prepare for a clinical study, the Company conducted several scientific advice meetings with the Medicines and Healthcare Products Regulatory Agency (MHRA), UK, to gain an understanding of the regulatory requirements to support a clinical trial application for PRP, to be conducted at the Peter Mac Cancer Center, in Melbourne, Australia. As a result of planning to undertake the first clinical study in Melbourne, Australia, a Certificate for Advance Overseas Finding was received from the Board of Innovation and Science Australia to receive up to a 43.5% "cash back" benefit from overseas R&D expenses. To qualify for the advance overseas finding, R&D expenditure incurred overseas will not exceed expenditure on local, Australian R&D activities, which will also receive up to a 43.5% cashback benefit. In other words, overseas vs. Australian R&D expenses must not exceed a 50:50 split.

The Company also achieved Orphan Drug Designation Status from the US Food& Drug Administration (FDA) for the treatment of pancreatic cancer, which means that the Company qualifies for seven-year FDA-administered market Orphan Drug Exclusivity (ODE), tax credits of up to 50% of R&D costs, R&D grants, waived FDA fees, protocol assistance and may get clinical trial tax incentives.

"Over the last decade, our R&D team has left no stone unturned in preparing for our upcoming milestone in entering the clinical development stage for PRP," said Mr. Nathanielsz. "When we completed some pivotal milestones, such as receiving future tax credits from the Australian Government, as well as achieving ODE status from the USFDA, provides me with confidence that we are on track to achieve success in our first clinical study, given that clinical data, as well as compelling scientific evidence, is normally required to receive such a designation. As a result, our IP asset pricing reflects a decent valuation, which contrasts significantly to our current market price as a publicly listed entity, which I believe can change when our important R&D milestones are achieved."

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.

Oncotelic Announces Presentation of P001- OT-101 Phase 1/2 Trial in Pancreatic Cancer

On July 12, 2022 Oncotelic Therapeutics, Inc. ("Oncotelic" or the "Company") (OTCQB:OTLC), developer of treatments for rare and orphan indications, including Parkinson Disease and various cancers, reported that the Company presentation at 7th JCA-AACR Special Joint Conference (July 8-10, 2022) is now available at View Source and View Source (Press release, Oncotelic, JUL 12, 2022, View Source [SID1234616616]).

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Key patient inclusion criteria
No longer amenable to established forms of therapy.
At least one measurable lesion
Karnofsky > 80%
Key findings
OT-101 PK is dose proportional (p<0.0001)
More than half of the OT-101 treated PC patients went into long term disease control (21 of 37 pts, 55%) allowing them to enter into subsequent chemotherapy which has an unexpected benefit of more than doubling their median OS, 9.3 vs. 2.6 mos, p<0.0001.
Among those who underwent subsequent chemotherapy, high AUC was associated with improved OS, 9.6 vs. 2.4 mos, p=0.0006

Leap Therapeutics Announces Initiation of New DKN-01 Clinical Trials in Gastric Cancer, Colorectal Cancer and Endometrial Cancer

On July 12, 2022 Leap Therapeutics, Inc. (NASDAQ: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, and BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and acc688235ess for patients worldwide, reported the initiation of Part C of the ongoing DisTinGuish study to evaluate DKN-01, Leap’s anti-SSEDickkopf 1 (DKK1) antibody, in combination with tislelizumab, BeiGene’s anti-PD-1 antibody, and chemotherapy compared to a tislelizumab and chemotherapy control arm, in patients with gastric or gastroesophageal junction cancer (G/GEJ) (Press release, Leap Therapeutics, JUL 12, 2022, View Sourcenews-releases/news-release-details/leap-therapeutics-announces-initiation-new-dkn-01-clinical" target="_blank" title="View Sourcenews-releases/news-release-details/leap-therapeutics-announces-initiation-new-dkn-01-clinical" rel="nofollow">View Source [SID1234616615]).

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Additionally, Leap is initiating a new company-sponsored trial of DKN-01 in combination with standard of care bevacizumab and chemotherapy in second-line patients with colorectal cancer that is designed to expand into a randomized study. Leap is also supporting an investigator-initiated trial of DKN-01 plus pembrolizumab in patients with endometrial cancer to be conducted at The University of Texas M.D. Anderson Cancer Center and at the University of Alabama at Birmingham.

Leap’s management team, together with key opinion leaders, will host an R&D Day today to provide updates on the Company’s DKN-01 program including G/GEJ, colorectal cancer, endometrial cancer, and prostate cancer.

"Since the presentation of the data for DKN-01 plus tislelizumab and chemotherapy in first-line G/GEJ patients demonstrating compelling overall response rates and progression-free survival, Leap and BeiGene have been working together to create an optimal global strategy for this unique combination therapy. We are excited to enhance the development program and our collaboration with BeiGene through a randomized controlled trial in first-line patients, with a focus on those patients whose tumors express high levels of DKK1," said Douglas E. Onsi, President and Chief Executive Officer of Leap.

"Based on our clinical and preclinical data, Leap is committed to developing DKN-01 aggressively in multiple indications," said Cynthia Sirard, MD, Chief Medical Officer of Leap. "Through a strategic review and prioritization process, we have decided to initiate a company-sponsored study in second-line colorectal cancer patients of DKN-01 in combination with standard of care bevacizumab and chemotherapy. We will also support an investigator-initiated study in endometrial cancer patients of DKN-01 in combination with pembrolizumab, building on previous data showing single-agent activity of DKN-01."

R&D DAY:
Leap’s management team will host an R&D Day today at 12:00 p.m. Eastern Time and will be joined by key opinion leaders:

Samuel Klempner, MD, Associate Professor at Harvard and Massachusetts General Hospital;
Zev Wainberg, MD, Co-Director of the GI Oncology Program at University of California Los Angeles;
Rebecca Arend, MD, Assistant Professor at University of Alabama at Birmingham Comprehensive Cancer Center; and
David Wise, MD, PhD, Assistant Professor at NYU Langone Health.

The live webcast presentation of the R&D Day can be accessed by registering at View Source A replay of the event will be available for a limited time and may be accessed on the Investors page of the Company’s website at View Source

GASTRIC CANCER
The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. Part C of the DisTinGuish study will enroll approximately 160 first-line, HER2-negative patients who have had no prior therapy for unresectable locally advanced or metastatic G/GEJ adenocarcinoma. Patients will be randomized 1:1 to study DKN-01 in combination with tislelizumab and SOC chemotherapy, compared to tislelizumab and SOC chemotherapy. The primary objective of Part C is progression-free survival (PFS) in patients whose tumors express high levels of DKK1 (DKK1-high). Secondary objectives of Part C include PFS in all patients regardless of DKK1 expression, as well as overall survival (OS) and objective response rate (ORR) as measured by RECIST v1.1 in DKK1-high and all patients.

Part A and Part B of the DisTinGuish study are currently being conducted in the United States and the Republic of Korea. Part A enrolled 25 first-line HER2- G/GEJ cancer patients. As of December 10, 2021, the median PFS for all patients in Part A was 10.7 months, with 11.9 months PFS for DKK1-high patients, and the ORR for all patients who had completed a full cycle of therapy was 68%, with 90% ORR for DKK1-high patients. Part B of the study has enrolled 51 patients with second-line DKK1-high G/GEJ cancer. Additional follow-up data from Part A is expected to be presented in the third quarter 2022 and from Part B in the fourth quarter 2022.

COLORECTAL CANCER
The DeFianCe study is a Phase 2 study of DKN-01 in combination with bevacizumab and SOC chemotherapy in patients with advanced colorectal cancer who have received one prior systemic therapy. The study is designed with an initial 20 patient cohort and to then expand into a 130 patient randomized controlled trial against bevacizumab and SOC chemotherapy. The primary objective is PFS. Secondary objectives include ORR, duration of response (DOR), and OS. The study is expected to enroll its first patient in the third quarter 2022.

ENDOMETRIAL CANCER
The investigator-initiated trial of DKN-01 in combination with pembrolizumab is an open-label, Bayesian design, Phase 2 trial and will initially enroll 15 patients each into DKK1-high and DKK1-low cohorts. If the efficacy criteria is met in either or both of the 15 patient cohort(s), then the cohort(s) will be expanded by an additional 15 patients. The primary objective of the study is ORR. Secondary objectives include clinical benefit rate (CBR), PFS, OS, and DOR. The study is expected to enroll its first patient in the fourth quarter 2022.

Leap has previously studied DKN-01 as a monotherapy and in combination with paclitaxel in patients with endometrial cancer. In the group of 23 patients treated with DKN-01 monotherapy for whom DKK1 expression data was available, patients with DKK1-high tumors achieved 1 complete response and 1 partial response, along with greater ORR (25% vs. 0%), CBR (63% vs. 7%), and median PFS (4.3 months vs. 1.8 months [HR 0.26; 95 CI: 0.09, 0.75]) compared to patients with DKK1-low tumors. In the group of 24 patients treated with DKN-01 plus paclitaxel, 72% of whom had received three or more prior systemic therapies, DKK1-high patients had improved median PFS (5.4 months vs. 1.8 months [HR 0.34; 95% CI: 0.12, 0.97]) compared to DKK1-low patients.

ABOUT DKN-01
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.

ABOUT THE LEAP/BEIGENE COLLABORATION
Leap is conducting the DisTinGuish study as part of an exclusive option and license agreement with BeiGene for the development of DKN-01 in Asia (excluding Japan), Australia, and New Zealand. Leap retains exclusive rights for the development, manufacturing, and commercialization of DKN-01 for the rest of the world.

Y-mAbs’ Announces Clearance of IND for GD2-SADA

On July 12, 2022 -mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported initiation of its first clinical trial with a SADA construct (Press release, Y-mAbs Therapeutics, JUL 12, 2022, View Source [SID1234616613]). This Phase 1 multicenter basket trial targets malignant melanoma, sarcoma and small cell lung cancer. The trial will have three parts: Part A with dose-finding for the SADA molecule and testing of dosing intervals between the protein and the 177Lu-DOTA payload, Part B will determine the optimal dose of 177Lu-DOTA, and Part C will be evaluating safety and initial signals of efficacy using repeated dosing. The Company expects a total of approximately 59 patients at 6-10 U.S. sites to be included in the trial.

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The GD2-SADA construct was created using our SADA technology, which was licensed by the Company from Memorial Sloan Kettering Cancer Center ("MSK") and Massachusetts Institute of Technology ("MIT") in April 2020. The SADA technology utilizes a pre-targeted payload delivery method where antibody constructs assemble in tetramers and bind to the tumor target. Unbound constructs predictably disassemble into smaller antibody fragments and are excreted through the kidneys within hours after administration. In a second infusion, a radioactive payload binds to the antibody constructs attached to the tumor target in order to radiate the tumor. This provides the possibility of targeting tumors with precision while minimizing radiation of normal tissues. We believe that the SADA technology platform can deliver a variety of payloads and could potentially be developed against multiple tumor targets, as well as for theragnostic purposes.

"The FDA acceptance of the IND for GD2-SADA marks an important milestone towards our mission of developing novel SADA treatments as we continue to execute our clinical development strategy for our pipeline of SADA constructs for the treatment of cancers with unmet medical need," said Thomas Gad, founder, President and Interim CEO. "We are seeing significant partnership interest for the SADA technology and we believe we are well-positioned to leverage the SADA platform as we move forward. We are truly excited about the potential of the SADA technology, which has already shown great promise, and we believe that it can further unlock the potential of radiolabeled therapeutics in tumors that have not historically demonstrated meaningful responses to radiolabeled agents."

Researchers at MSK, including Dr. Cheung, developed the SADA technology for radioimmunotherapy, which is exclusively licensed by MSK to Y-mAbs. Dr. Cheung has intellectual property rights and interests in the technology, and as a result of this licensing arrangement, MSK has institutional financial interests in the technology and in Y-mAbs.

Sutro Biopharma Announces Virtual Deep Dive Research Forum: Next-Gen Innovations in ADCs

On July 12, 2022 Sutro Biopharma, Inc. ("Sutro" or the "Company") (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported that management will host a virtual research forum in which it will unveil the next product candidate, discuss immunostimulatory ADCs (iADCs) as a novel modality, and highlight recent enhancement to its cell-free manufacturing platform (Press release, Sutro Biopharma, JUL 12, 2022, View Source [SID1234616612]).

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Webcast details:

Wednesday, July 20, 2022 at 4:30 pm ET, or 1:30 pm PT
To access and register for the live webcast, please go to View Source
The webcast information will also be available through the News & Events section of the Investor Relations portion of the Company’s website at www.sutrobio.com. An archived replay will be available for at least 30 days after the event.