December 2020 – Page 84 – 1stOncology™: Cancer Intelligence Service

Kazia to Collaborate with Pacific Pediatric Neuro-Oncology Consortium (PNOC) for New Paxalisib Combination Study in DIPG

On December 10, 2020 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported that it has executed a Letter of Intent with the Pacific Pediatric Neuro-Oncology Consortium (PNOC) to launch a clinical trial of multiple therapies, including Kazia’s investigational new drug, paxalisib (formerly GDC-0084), in diffuse midline gliomas including diffuse intrinsic pontine glioma (DIPG) (Press release, Kazia Therapeutics, DEC 10, 2020, View Source [SID1234572773]).

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 new clinical trial, PNOC022, will employ an adaptive trial design to test several therapies in different combinations and in different subsets of patients. In addition to paxalisib, the other therapies involved will initially include ONC201, manufactured by Oncoceutics, Inc, and panobinostat, manufactured by SecuraBio, Inc. The study is expected to open initially in the United States and will then expand to other countries during CY2021.

Key Points

PNOC022 uses cutting-edge clinical trial design to efficiently and rapidly evaluate combination therapies in DIPG, under the leadership of world experts in the field
Lead investigator is Professor Sabine Mueller, a leading paediatric neuro-oncologist and co-founder of PNOC
Study is guided by Australian research at University of Newcastle, under leadership of Associate Professor Matt Dun, who serves as a scientific advisor
Combination approach builds on recent positive data from St Jude SJPI3K study (NCT03696355) with paxalisib as single agent in DIPG, and brings together several of the most promising candidates in the global pipeline for DIPG
Kazia will provide paxalisib investigational product; study is fully funded by PNOC
Kazia CEO, Dr James Garner, commented, "DIPG and diffuse midline gliomas have emerged as an exciting second front in the development of paxalisib as a brain cancer therapy. Work by Dr Chris Tinkle and colleagues at St Jude Children’s Research Hospital has taught us a great deal about how to use this drug in a paediatric population. In parallel, extensive laboratory research by Associate Professor Matt Dun and colleagues has generated a rich and comprehensive data set to inform combination use. We are delighted to now have the opportunity to work with the PNOC team to bring these insights together and to take paxalisib into the next chapter of its development as a potential therapy for DIPG."

Clinical Trial Design

PNOC022 will enrol children and young adults with diffuse midline gliomas, a category of brain tumours that includes DIPG. The study will include separate cohorts comprising patients with newly diagnosed disease, patients who have completed initial radiotherapy, and patients who have experienced disease progression after treatment.

At the outset, all patients will be treated with ONC201, combined with either paxalisib or panobinostat. The study employs an adaptive design, in which different arms will opened and closed based on emerging preclinical and clinical data. The primary endpoint will be the proportion of patients progression-free at six months (PFS6) for newly diagnosed patients, and overall survival (OS) for recurrent patients.

The lead investigator will be Professor Sabine Mueller, a board-certified neurologist and paediatric neuro-oncologist whose research focuses on novel therapies in childhood brain cancer. Professor Mueller holds an academic appointment in the Department of Neurology, Neurosurgery and Pediatrics at the University of California, San Francisco (UCSF) and serves as head of the clinical programme at the DMG Centre at the Children’s Hospital of the University of Zurich. She obtained her medical degree from the University of Hamburg, and also holds a PhD in molecular biology.

Professor Mueller commented, "DIPG remains one of the most challenging of childhood cancers. No drug treatment has ever demonstrated meaningful efficacy. The PNOC022 study brings a different approach, uniting the best of preclinical research with novel clinical trial techniques. We look forward to commencing enrolment to the study shortly, and very much hope that we are able to generate new hope for patients and their families."

Commencement of the study remains subject to execution of a definitive contract and is dependent on approval by the US FDA and Institutional Review Boards. It is expected that PNOC022 will initially open in the United States in 1H CY2021, with expansion to other countries taking place in CY2021. Discussions are ongoing regarding the potential inclusion of Australian sites in the study.

Australian Scientific Research

The design of the PNOC022 study has been extensively informed by laboratory research in DIPG, and in particular by research undertaken at the University of Newcastle, Hunter Medical Research Institute (HMRI) by Associate Professor Matt Dun and colleagues. The HMRI team has conducted laboratory research with paxalisib for several years and has generated a powerful body of data combining paxalisib with other investigational drugs. This research has been partly funded by RUN DIPG, a not-for-profit organisation led by Associate Professor Dun, the DIPG Collaborative, Defeat DIPG Michael Moiser Foundation and the McDonald Jones Foundation. The robust mechanistic data is expected to be published in high impact scientific journals in coming months.

Pacific Pediatric Neuro-Oncology Consortium (PNOC)

The Pacific Pediatric Neuro-Oncology Consortium (PNOC) is an international consortium, with study sites in the United States, Canada, Swizterland, Europe, India, Israel, and Australia. PNOC is dedicated to bringing new therapies to children and young adults with brain tumours, using the latest scientific understanding to inform a personalised medicine approach.

PNOC comprises 225 leading specialists in childhood brain cancer and is currently driving sixteen international clinical trials. In Australia, the organisation collaborates closely with the Australia and New Zealand Children’s Hematology / Oncology Group (ANZCHOG). PNOC’s research is substantially supported by the PNOC Foundation, the Pediatric Brain Tumor Foundation, and other not-for-profit entities.

Paxalisib Clinical Program

The initiation of this trial will bring the number of ongoing clinical studies of paxalisib in brain cancer to eight.

Indication

Phase

Sponsor

Registration

Glioblastoma

Kazia Therapeutics

NCT03522298

Glioblastoma

II / III

Global Coalition for Adaptive Research

NCT03970447

DIPG & DMGs

St Jude Children’s Research Hospital

NCT03696355

DIPG & DMGs

N/A*

Pacific Pediatric Neuro-Oncology Consortium

(TBD)

Breast Cancer Brain Metastases

Dana-Farber Cancer Institute

NCT03765983

Brain Metastases

Alliance for Clinical Trials in Oncology

NCT03994796

Brain Metastases

Memorial Sloan-Kettering Cancer Center

NCT04192981

Primary CNS Lymphoma

Dana-Farber Cancer Institute

(TBD)

*Note – the PNOC022 has not adopted a ‘phase’ designation and is described as an ‘adaptive platform study’

Next Steps

Recruitment to this study is expected to commence in 1H CY2021.

Protagonist Therapeutics, Inc. Announces Pricing of $100 Million Public Offering of Common Stock

On December 10, 2020 Protagonist Therapeutics, Inc. (Nasdaq: PTGX), a clinical stage biopharmaceutical company, reported the pricing of its previously announced underwritten public offering of 4,761,904 shares of its common stock at a price to the public of $21.00 per share (Press release, Protagonist, DEC 10, 2020, View Source [SID1234572710]). Gross proceeds to Protagonist from the offering are expected to be $100 million, before deducting underwriting discounts and commissions and offering expenses. All of the shares of common stock are being offered by Protagonist. In addition, Protagonist has granted the underwriters a 30-day option to purchase up to 714,285 additional shares of common stock at the public offering price, less underwriting discounts and commissions. The offering is expected to close on or about December 15, 2020, subject to satisfaction of customary closing conditions.

J.P. Morgan Securities LLC, SVB Leerink LLC, Piper Sandler & Co. and BMO Capital Markets Corp. are acting as joint book-running managers for the offering.

A shelf registration statement relating to the offered shares of common stock was filed with the Securities and Exchange Commission (SEC) on December 10, 2020. A preliminary prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and a final prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC and will be available on the SEC’s website, located at www.sec.gov. The offering is being made only by means of a prospectus supplement and accompanying prospectus. Copies of the prospectus supplement and the accompanying prospectus related to the offering may be obtained, when available, from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6132 or by email at [email protected]; from Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924 or by email at [email protected]; or from BMO Capital Markets Corp., Attention: Equity Syndicate Department, 3 Times Square, 25th Floor, New York, NY 10036, by telephone at (800) 414-3627 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Underwriting Agreement

On December 10, 2020, Protagonist Therapeutics, Inc. ("Protagonist" or "the Company") reported that it entered into an underwriting agreement (the "Underwriting Agreement") with J.P. Morgan Securities LLC, SVB Leerink LLC and Piper Sandler & Co., as representatives of the several underwriters named therein (collectively, the "Underwriters"), relating to the public offering, issuance and sale of 4,761,904 shares of the Company’s common stock, par value $0.00001 per share ( the "Common Stock") (Filing, 8-K, Protagonist, DEC 10, 2020, View Source [SID1234572654]). The price to the public in this offering is $21.00 per share, and the Underwriters have agreed to purchase the shares from the Company pursuant to the Underwriting Agreement at a price of $19.74 per share. Under the terms of the Underwriting Agreement, Protagonist also granted the Underwriters an option exercisable for 30 days to purchase up to an additional 714,285 shares of Common Stock at the public offering price, less underwriting discounts and commissions. The gross proceeds to the Company from this offering are expected to be approximately $100.0 million, before deducting underwriting discounts and commissions and other estimated offering expenses payable by the Company, or $115.0 million if the Underwriters exercise in full their option to purchase additional shares of Common Stock. The offering is expected to close on December 15, 2020, subject to customary closing conditions.

The Underwriting Agreement contains customary representations, warranties and agreements by the Company, customary conditions to closing, indemnification obligations of the Company and the Underwriters, including for liabilities under the Securities Act of 1933, as amended, other obligations of the parties and termination provisions. The representations, warranties and covenants contained in the Underwriting Agreement were made only for purposes of such agreement and as of specific dates, were solely for the benefit of the parties to such agreement, and may be subject to limitations agreed upon by the contracting parties, including being qualified by confidential disclosures exchanged between the parties in connection with the execution of the Underwriting Agreement.

The offering is being made pursuant to the Company’s effective registration statement on Form S-3ASR and an accompanying prospectus (Registration Statement No. 333-251254) previously filed with the SEC and a preliminary and final prospectus supplement thereunder.

The Underwriting Agreement is filed as Exhibit 1.1 to this report, and the description of the terms of the Underwriting Agreement is qualified in its entirety by reference to such exhibit. A copy of the opinion of Cooley LLP relating to the legality of the issuance and sale of the shares in the offering is attached as Exhibit 5.1 hereto.

Immutep Reports Statistically Significant Survival Benefit for Key Patient Groups in the Ongoing Phase IIb AIPAC Study in Metastatic Breast Cancer

On December 10, 2020 Immutep Limited (ASX: IMM; NASDAQ: IMMP) a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune disease, reported encouraging first Overall Survival (OS) follow up data from its ongoing Phase IIb AIPAC study evaluating Immutep’s lead product candidate eftilagimod alpha in combination with paclitaxel chemotherapy ("efti group") in comparison to a combination of placebo and paclitaxel chemotherapy ("comparator group") in patients with HER2-negative/HR positive metastatic breast cancer (HR+ MBC) (Press release, Immutep, DEC 10, 2020, View Source [SID1234572650]). These data were selected to be presented in a spotlight presentation at the San Antonio Breast Cancer Symposium 2020, which is being held virtually this week from Texas, USA.

AIPAC Principal Investigator, Hans Wildiers of University Hospital Leuven, Leuven, Belgium, said:

"Improving Overall Survival is a key endpoint when evaluating the benefit of new anticancer drugs. Efti is a new drug targeting the immune system in an innovative way and has the potential to improve outcomes in HER2-negative/hormone receptor positive metastatic breast cancer patients. The AIPAC study investigated efti in combination with first line chemotherapy in this population, a group of about 250,000 patients diagnosed worldwide each year. Although the progression free survival data in the efti group did not show a significant improvement versus the comparator arm in AIPAC earlier this year, the OS data in general looks already very interesting and will mature further. The OS data in subgroups such as those below age 65 years are highly encouraging and may lead to more effective treatment options for metastatic breast cancer patients."

Immutep CSO and CMO, Dr Frederic Triebel said: "We are very excited to see that efti is boosting the immune system by providing a statistically significant increase in CD8 T cell numbers, which is correlated with prolonged survival for patients. These data provide proof-of-concept and support our long-held belief that efti can provide a meaningful benefit to patients in a range of cancer settings by "pushing the

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

LOGO

gas" on the body’s immune system, representing an important landmark. Through this mechanism, efti is helping a large proportion of patients in the AIPAC study with Her2-HR+ metastatic breast cancer which is typically a non-immunogenic cancer and is therefore significantly less responsive to modern immune checkpoint inhibitor (ICI) therapies. As such, chemotherapy continues to be the standard of care in many instances and there continues to be a large unmet medical need. We look forward to reporting final survival data in 2021."

Immutep CEO, Marc Voigt said: "AIPAC marks an important milestone for Immutep and builds our confidence that efti is beneficial for many cancer patients, including those with metastatic breast cancer. Notably, we have seen a more material OS benefit than PFS benefit in this study; however, we note that this is not unusual for some immunotherapies where it can take time for the body’s immune system to be boosted and provide a therapeutic benefit. We are very encouraged by these first OS results which, subject to ongoing data collection, warrant a registrational perspective and regulatory interactions towards what we hope will be an important new class of medicines."

Key Efficacy Results: data cut-off 24 September 2020

In the total patient population, first OS data (based on approx. 60% of events) show that patients in the efti group had an improving OS trend with a median OS of 20.2 months compared to 17.5 months for patients in the comparator group, indicating a survival benefit of +2.7 months (HR = 0.83; p = 0.14). The OS analysis is based on a 2-sided false positive probability of 0.05. Furthermore, a significant deterioration in quality of life was observed for patients in the comparator group at week 25, which was not observed in the efti group. This is an encouraging observation as these types of benefits are supportive of efti being eligible for reimbursement upon marketing approval.

In key predefined patient groups, the study has already demonstrated a statistically significant and clinically relevant OS benefit from treatment with efti in combination with chemotherapy. Patients under the age of 65 years (representing 66.7% of patients in the efti group) reported a median OS of 21.9 months compared to 14.8 months in the comparator group, indicating a survival benefit of +7.1 months (HR = 0.62; p = 0.012) favoring the efti group.

Figure 1 – Kaplan Meyer curve OS for patients < 65 years

The current data suggest that for patients younger than 65 years old, the probability of being alive at three years with efti plus chemotherapy vs. chemotherapy alone is increased by 100%.

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

Furthermore, patients with a low monocyte count at baseline (representing 21.9% of patients in the efti group) reported a median OS of 22.4 months compared to 12.9 months in the comparator group, indicating a survival benefit of +9.4 months (HR = 0.47; p = 0.02) favoring the efti group.

Trending towards statistical significance, patients with a more aggressive, more immunogenic luminal B type of breast cancer (representing 48.8% of patients in the efti group) reported a median OS of 16.3 months compared to 12.6 months in the comparator group, indicating a beneficial trend of +3.8 months (HR = 0.69; p = 0.077) favoring the efti group. (See Table 1)

Table 1 – Overall Survival in key patient groups

Note: A lower HR, means a reduced risk of death, e.g. by 53% in the low monocyte group.

Immuno Monitoring Results

Importantly, there was a statistically significant, sustained long-term increase in peripheral CD8 T cells in patients in the efti group. This is consistent with the mode of action of efti. There was also a statistically significant correlation between those patients having an increase in the number of CD8 T cells and those having a prolonged OS. This represents a strong proof-of-concept in a randomised, double blinded setting.

Safety

The combination of efti and paclitaxel chemotherapy was overall safe and well tolerated, further building upon efti’s strong safety profile to date.

The presentation poster is available at www.immutep.com/investors-media/presentations.html.

Next Steps

Multivariate analysis of the data is ongoing and final OS data is expected to be reported in mid 2021.

Webcast Details

Immutep will present this AIPAC data in a global webcast for investors, details are as follows:

•
Date & Time: Friday, 11 December 2020, at 8.30 am Australian Eastern Daylight Time (AEDT) (Thursday, December 10th, at 4:30 p.m. U.S. ET)

Register: View Source

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

Questions: Investors are invited to submit questions in advance via [email protected].

A replay of the webcast will also be available at www.immutep.com from the day after the event.

About the AIPAC trial

Active Immunotherapy Paclitaxel (AIPAC) is a multicentre, placebo-controlled, double-blind, 1:1 randomised Phase IIb clinical trial in HER2-negative/HR positive metastatic breast cancer.

The study is evaluating the combination of Immutep’s lead product candidate, eftilagimod alpha (efti, LAG-3Ig or IMP321), and paclitaxel chemotherapy. 227 HER2-negative/HR positive metastatic breast cancer patients are randomised 1:1 to a chemo-immunotherapy arm (efti plus paclitaxel) or to a comparator arm (placebo plus paclitaxel). Patients receive weekly paclitaxel at days 1, 8 and 15, with either efti or placebo injected subcutaneously on days 2 and 16 of each 4-week cycle, repeated for 6 cycles. Thereafter, patients pass over to the maintenance phase with efti alone.

Kitov Announces Name Change to Purple Biotech Ltd.

On December 10, 2020 Purple Biotech Ltd. (the "Company") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported that it has changed its corporate name from Kitov Pharma Ltd. to Purple Biotech Ltd (Press release, Kitov Pharmaceuticals , DEC 10, 2020, View Source [SID1234572643]). The name change will be effective for trading purposes on the Tel Aviv Stock Exchange (TASE) and the NASDAQ Capital Market (NASDAQ) as of market open on December 22, 2020. At that time, the Company’s ordinary shares and American Depositary Shares (ADSs) will begin to trade under the new ticker symbol, "PPBT," on the TASE and NASDAQ, respectively. The Company’s ordinary shares will continue to trade on the TASE and its ADSs will continue to trade on NASDAQ under the ticker symbol "KTOV" through market close on December 21, 2020. The Company’s ADSs were assigned a new CUSIP number (74638P109), effective on December 22, 2020, as described above.

"Over the past few years, our business has evolved significantly towards an exciting new vision and our new name, Purple Biotech, completes the transformation to our focus on advancing first-in-class oncology therapies," said Isaac Israel, the Company’s Chief Executive Officer.

"2020 has been a year of substantial achievements for our company. We recently initiated Phase 1/2 clinical studies for NT219 and expect to begin our Phase 1/2 studies for CM24 shortly. We also successfully completed over $60 million in financings this year to support our clinical development and strategic plans. As we head into 2021, we look forward to leveraging the compelling opportunities that lie ahead of us and to advancing our objectives to increase the longevity and the quality of life of cancer patients", added Isaac Israel.

The Company will also be relocating its corporate headquarters shortly to the Science Park near the Weizmann Institute in Rehovot, Israel, a key regional biotech hub.

No action is required by shareholders and holders of ADSs in connection with the corporate name change. The number of outstanding ordinary shares and ADSs are not affected by the name change. In connection with the name change, the Company expects to make additional ordinary course filings with the U.S. Securities and Exchange Commission.

1stOncology is recognized as a
Top 10 Global Pharma Analytic Provider

Continue your journey with 1stOncology by accessing our Free Leading Cancer Conference Whitepapers, signing up for our Free Weekly Newsletter and requesting a Free Demo to see how we can help you be 1st in Oncology!

Month: December 2020

Kazia to Collaborate with Pacific Pediatric Neuro-Oncology Consortium (PNOC) for New Paxalisib Combination Study in DIPG

Protagonist Therapeutics, Inc. Announces Pricing of $100 Million Public Offering of Common Stock

Underwriting Agreement

Immutep Reports Statistically Significant Survival Benefit for Key Patient Groups in the Ongoing Phase IIb AIPAC Study in Metastatic Breast Cancer

Kitov Announces Name Change to Purple Biotech Ltd.