Case Western Reserve dental school researcher awarded $3.7M in NIH grants to study link between people living with HIV and higher rates of cancer and other diseases

On January 27, 2022 Case Western Reserve University reported that About 1.2 million people with HIV in the United States live relatively normal lives with uncompromised immune systems and the virus medically controlled (Press release, Case Western Reserve University, JAN 27, 2022, View Source [SID1234607435]).

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But there are two rising concerns, said Ge Jin, a professor in the Department of Biological Sciences at the Case Western Reserve University School of Dental Medicine.

"One, they are aging and will develop all the diseases or illnesses of the general population, like you or me," he said. "The other problem—those morbidities, like cancer or co-infection with other viruses, happen at an earlier stage, occur at a higher rate and are more severe (for people with HIV)."

With two new research grants totaling $3.7 million from the National Institutes of Health (NIH), Jin and his co-investigators hope to learn why.

The new grants will focus on identifying the reasons for higher rates of cancers in the head and neck within this population, as well as co-infection with the herpes virus (Kaposi sarcoma herpesvirus or KSHV).

Jin, also a member of the Case Comprehensive Cancer Center’s Molecular Oncology Program, received:

A five-year, $3.3 million grant from the National Cancer Institute at NIH to investigate the mechanisms underlying transmission of KSHV in the oral cavity in people living with HIV.
KSHV causes Kaposi sarcoma (KS), one of the most common malignancies in people living with HIV. While the oral cavity contains the highest levels of infectious KSHV—and saliva is the most common way to transmit the infection—how that happens isn’t understood.

Jonathan Karn, professor and chair of the Department of Molecular Biology and Microbiology at the School of Medicine and director of the Case Center for AIDS Research, is co-investigator on this project.

A related $401,000 grant from the National Institute of Dental and Craniofacial Research at NIH to study why cases of oral diseases, like lesions that could develop into oral cancers, are increasing as people with HIV age—and then identify new therapies. Michael Lederman, professor emeritus at the School of Medicine, is co-investigator.
This new round of funding builds on a $3.7 million grant Jin and his research team received from NCI in July 2020 to study HIV and lung cancer—specifically why lung cancer rates are higher for people living with HIV, and the mechanism and markers to predict and treat the disease.

HIV infects immune cells; cancers in the lung and oral cavity affect epithelial cells. If researchers can figure out the link between HIV and higher cancer rates—and how to break that connection—then the next step would be to focus on therapies to treat the diseases.

"The first thing is," Jin said, "identifying how and why they can talk with each other."

Sierra Oncology to Present at B. Riley Securities Oncology Investor Conference

On January 27, 2022 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage biopharmaceutical company dedicated to delivering targeted therapies for rare cancers, reported the company will participate in the 2022 B. Riley Securities Oncology Investor Conference being held virtually from January 27-28, 2022 (Press release, Sierra Oncology, JAN 27, 2022, View Source [SID1234607452]). President and Chief Executive Officer Stephen Dilly, MBBS, PhD, will provide an overview of the company at 2:30 pm ET on Friday, January 28, 2022.

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A replay of the presentation will be available following the conference on the Investors section of Sierra’s corporate website in the Events & Webcast tab. The replay will be available for approximately 30 days following the presentation.

Oncolytics Biotech® Partner Adlai Nortye Advances to the Second Dose Escalation Cohort of the Chinese Bridging Trial Evaluating Pelareorep-Paclitaxel Combination Treatment in Breast Cancer

On January 27, 2022 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported that its partner Adlai Nortye has advanced to the second of three dose escalation cohorts in the bridging clinical trial evaluating the safety, tolerability, and preliminary efficacy of pelareorep-paclitaxel combination therapy in Chinese patients with advanced or metastatic breast cancer (Press release, Oncolytics Biotech, JAN 27, 2022, View Source [SID1234607436]). Dosing in the trial’s first dose escalation cohort is complete and no safety issues have been reported. The second dose escalation cohort is the equivalent dose that was administered in the IND-213 study, which reported a near doubling of survival in HR+/HER2- metastatic breast cancer patients.

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"Initiation of the bridging trial’s second dose escalation cohort is an important advancement that reflects the positive safety findings observed in the trial to date," said Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development. "Completion of the bridging trial will allow future Chinese regulatory submissions that will include previously reported clinical data demonstrating pelareorep’s potential to substantially benefit metastatic breast cancer patients. This may accelerate pelareorep’s development in rapidly growing pharmaceutical markets such as China, which is the second largest in the world after the United States. Looking ahead, we will continue to collaborate closely with Adlai Nortye to advance pelareorep towards registration in these jurisdictions and maximize its potential therapeutic impact."

The bridging clinical trial is designed to satisfy Chinese regulatory requirements and thereby accelerate pelareorep’s development in territories that include China, Hong Kong, and Macau. Results from the trial are expected to allow Adlai Nortye to include data from Oncolytics’ randomized North American metastatic breast cancer trials in future submissions to regulators in China and its territories.

The first of Oncolytics’ randomized North American trials, IND-213, showed a statistically significant near doubling of overall survival in patients treated with pelareorep and paclitaxel compared to those treated with paclitaxel alone. Oncolytics’ second randomized North American trial, BRACELET-1, is ongoing and evaluates pelareorep-paclitaxel combination therapy both with and without a checkpoint inhibitor. Oncolytics expects to complete enrollment in BRACELET-1 later this quarter and to report top-line data from the trial in Q4. Oncolytics believes completion of BRACELET-1 represents the last major clinical step on pelareorep’s path to a registrational study in metastatic breast cancer in the United States.

About Breast Cancer
Breast cancer is the most common cancer in women worldwide, with over two million new cases diagnosed in 2018, representing about 25 percent of all cancers in women. It is the second leading cause of death from cancer in women in America, with an estimated 42,000 deaths in the U.S. in 20201. In China, breast cancer is now estimated to be the largest subtype of cancer among women, with over 416,000 cases and over 117,000 deaths in 20202.

Breast cancer starts when cells in the breast begin to grow out of control. These cells usually form a tumor that can often be seen on an x-ray or felt as a lump. The malignant tumor (cancer) gets worse when the cells grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body.

Perimeter Medical Imaging AI Announces Closing of Strategic Private Placement to Social Capital

On January 27, 2022 Perimeter Medical Imaging AI, Inc. (TSX-V:PINK)(OTC:PYNKF) (FSE:4PC) ("Perimeter" or the "Company"), a medical technology company driven to transform cancer surgery with ultra-high-resolution, real-time, advanced imaging tools to address high unmet medical needs, reported the closing of its previously announced private placement of units (each, a "Unit") for gross proceeds of C$48.7 million to the Company (the "Private Placement") (Press release, Perimeter Medical Imaging AI, JAN 27, 2022, View Source [SID1234607453]). The Private Placement included the C$43.4 million strategic investment in the Company (the "Investment") by Social Capital.

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Jeremy Sobotta, Perimeter’s Chief Executive Officer stated, "We are extremely excited to have completed this transformative, pivotal event for Perimeter and to welcome Social Capital as a shareholder of Perimeter. This strategic partnering with Social Capital comes at a time when we are ramping up our Perimeter S-Series market development activities and commercialization efforts across the U.S., while also supporting the ongoing clinical development of our next-gen AI technologies. We are very optimistic that the Private Placement will allow the Company to unlock additional growth and potential and we thank Social Capital for its support and endorsement of our vision to transform cancer surgery with ultra-high resolution, real-time, advanced imaging tools."

Chamath Palihapitiya, founder and CEO of Social Capital, said, "Perimeter has the opportunity to change how we approach removing cancerous tumors from the body. Starting with breast cancer, Perimeter’s OCT technology can potentially eliminate the need for a second or sometimes even third surgery because not all of the cancer was removed the first time – a risk faced by 1 in 4 breast cancer patients in America today. Over time, we hope Perimeter can apply this technology to a range of other tumor removal surgeries. We are excited to begin this partnership with Jeremy and his team to raise the standard of care for cancer patients."

Details Regarding the Private Placement

The Private Placement was completed on a non-brokered basis for gross proceeds of C$48.7 million at a price of C$3.00 per Unit for a total of 16,234,333 Units. Each Unit consisted of one common share (each, a "Common Share") and a total of one warrant ("Warrant") to purchase an additional Common Share (a "Warrant Share"). 80% of the Warrants issued in the Private Placement have a strike price of C$3.99 and 20% of the Warrants issued in the Private Placement have a strike price of C$4.50. Half of the Warrants at each strike price are subject to accelerated expiry if the 60-day volume weighted average trading price of Perimeter’s Common Shares is greater than the strike price during the applicable period. The other half of the Warrants are not subject to accelerated expiry, and instead they may be exercised for cash or exercised using a cashless exercise feature at any time prior to expiry. Subject to the accelerated expiry clause described above, all Warrants will expire five years following the closing of the Private Placement.

As the result of its C$43.4 million Investment, Social Capital acquired 14,466,667 Common Shares and 14,466,664 Warrants. Social Capital and Perimeter have also entered into an investor rights agreement whereby Social Capital will have the right to nominate one director to the board of Perimeter, as well as anti-dilution rights to participate in future financings, and customary registration rights. Social Capital’s board nomination and anti-dilution rights under the investor rights agreement will last so long as Social Capital holds at least 15% of the Common Shares of Perimeter on an undiluted basis, and Social Capital’s registration rights will last so long as Social Capital holds at least 10% of the Common Shares of Perimeter on an undiluted basis.

On a non-diluted basis, Social Capital now holds approximately 23.3% of the outstanding Common Shares making Social Capital a "Control Person" (as that term is defined in the policies of the TSX Venture Exchange (the "TSXV")) of Perimeter. The Investment by Social Capital was consented to in writing by shareholders of Perimeter holding greater than 50% of Perimeter’s outstanding Common Shares at the time the Private Placement was announced, including Roadmap Capital Inc., Perimeter’s largest shareholder, which entered into a support agreement in favour of the Private Placement at the time the Private Placement was announced.

In addition to the Investment by Social Capital, the Company issued an additional 1,767,666 Units to other investors for gross proceeds of C$5.3 million (resulting in aggregate gross proceeds of C$48.7 million).

The net proceeds of the Private Placement will be used for working capital, commercialization of Perimeter’s technology, clinical studies and the further development of Perimeter’s technology, and general corporate purposes.

All Common Shares and Warrants issued pursuant to the Private Placement will be subject to a statutory hold period of four months plus one day which expires on May 27, 2022.

In connection with the Closing of the Private Placement, the Company paid a finder’s fee equal to 3% of the proceeds from the sale of Units to Social Capital by issuing 434,000 Common Shares (the "Finder’s Shares") at a deemed price of $3.00 per Common Share. The Company also paid finder’s fees equal to 6% of the proceeds from the sale Units to certain investors introduced to Perimeter by other finders by paying cash in the amount of C$197,399.88.

The Common Shares comprising part of the Units, the Warrants and the Warrant Shares (if such Warrant Shares are issued before the date that is four months and one day following the applicable Closing Date) and the Finder’s Shares shall be subject to a hold period ending on the date that is four months and one day following the applicable Closing Date.

Insider Participation in the Private Placement

Jeremy Sobotta, Chief Executive Officer; Tom Boon, Chief Operating Officer; Andrew Berkeley, Vice President, Business Development; Aaron Davidson, Director; and Suzanne Foster, Director participated in the Private Placement, thereby making the Private Placement a "related party transaction" as defined under Multilateral Instrument 61-101 – Protection of Minority Security Holders in Special Transactions ("MI 61-101"). Mr. Sobotta subscribed for 10,000 Units, Mr. Boon subscribed for 5,000 Units, Mr. Berkeley subscribed for 6,000 Units, Mr. Davidson subscribed for 84,000 Units and Ms. Foster subscribed for 42,000 Units.

Each Common Share of Perimeter provides the holder with the right to one vote per common share. The Private Placement was unanimously approved by the directors of Perimeter and consented to by shareholders of Perimeter holding approximately 50.8% of Perimeter’s outstanding Common Shares at the time the Private Placement was announced.

Other than the subscription agreements between Mr. Sobotta, , Mr. Boon, Mr. Berkeley, Mr. Davidson and Ms. Foster relating to the issuance of the Units pursuant to the Private Placement, Perimeter has not entered into any agreement with an interested party or a joint actor with an interested party in connection with the Private Placement.

The Private Placement was exempt from the formal valuation and minority shareholder approval requirements of MI 61-101 as the Private Placement was a distribution of securities for cash and neither the fair market value of the Shares distributed to, nor the consideration received from, interested parties exceeded $2,500,000. Neither Perimeter, nor to the knowledge of Perimeter after reasonable inquiry, a related party, has knowledge of any material information concerning Perimeter or its securities that has not been generally disclosed. The material change report in connection with the Private Placement was not filed 21 days in advance of the closing of the Private Placement for the purposes of Section 5.2(2) of MI 61-101 on the basis that the subscriptions under the Private Placement were not available to Perimeter until shortly before the closing.

Early Warning Disclosure as a Result of Completion of the Investment

Pursuant to the Investment, Social Capital acquired 14,466,667 Common Shares and 14,466,664 Warrants. Prior to the completion of the Investment Social Capital did not own any Common Shares. On a non-diluted basis, Social Capital has increased its ownership of Common Shares from 0% to approximately 23.2%. On a partially-diluted basis, assuming exercise of the Warrants held by Social Capital, Social Capital exercises control over 28,933,331 (approximately 37.7%) of the issued and outstanding Common Shares.

As noted above, the Common Shares comprising part of the Units, the Warrants and the shares underlying the Warrants (if such shares are issued before the date that is four months and one day following the applicable closing date) held by Social Capital are subject to a four month plus one day hold period which expires on May 27, 2022.

Social Capital has acquired the Common Shares and Warrants for investment purposes.

The foregoing disclosure is being disseminated pursuant to National Instrument 62-103 – The Early Warning System and Related Take-Over Bid and Insider Reporting. A copy of the report to be filed with Canadian securities regulators in connection with the acquisition of these securities will be available on Perimeter’s SEDAR profile at www.sedar.com and a copy may be obtained by contacting Perimeter as noted under "Contact" below.

Preclinical Data Show Potential for Use of Genprex’s ONCOPREX® Nanoparticle Delivery System in Treating Colon Cancer

On January 27, 2022 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its collaborators published positive preclinical data for the use of Genprex’s ONCOPREX Nanoparticle Delivery System for delivery of a FAS DNA plasmid to treat metastatic colorectal cancer. Published in the journal Cancers1, the preclinical study found that tumor selective ONCOPREX nanoparticles carrying FAS DNA plasmids suppress human colon tumor growth in vivo in mouse models, indicating that this may be an effective therapy for human colorectal cancer (Press release, Genprex, JAN 27, 2022, View Source [SID1234607437]).

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The manuscript, "Restoring FAS Expression via Lipid-Encapsulated FAS DNA Nanoparticle Delivery Is Sufficient to Suppress Colon Tumor Growth In Vivo," provides data indicating that complete loss of FAS expression is often observed in metastatic human colorectal tumors. Using Genprex’s ONCOPREX system to deliver the FAS gene, the researchers found that overexpression of codon usage-optimized FAS in metastatic mouse colon-tumor cells enabled FASL-induced elimination of FAS positive tumor cells in vitro, suppressed colon tumor growth, and increased the survival of tumor-bearing mice in vivo.

"These positive preclinical data validate that the ONCOPREX Nanoparticle Delivery System can be used to deliver tumor suppressor genes other than TUSC2, which we are using in lung cancer studies with REQORSA, to address multiple types of cancer," said Mark S. Berger, MD, Chief Medical Officer at Genprex. "The data also provide early support for FAS as a tumor suppressor gene in colorectal cancer. With this compelling data, Genprex is positioned to expand its oncology programs in the future and to further explore use of its delivery system for other therapeutic genes, alone or in combination with other approved cancer therapies, to provide new therapeutic approaches for patients with serious medical conditions and unmet medical needs. We will continue to evaluate FAS using our ONCOPREX delivery platform as a potential pipeline addition within our oncology program."

Genprex’s oncology program utilizes its unique, proprietary, non-viral ONCOPREX Nanoparticle Delivery System, which is the first systemic gene therapy delivery platform used for cancer in humans.

The ONCOPREX delivery system is used to deliver TUSC2 plasmid DNA in Genprex’s REQORSA immunogene therapy. REQORSA is being combined with Tagrisso (by AstraZeneca) in the Company’s Acclaim-1 clinical trial and is being combined with Keytruda (by Merck & Co.) in the Company’s Acclaim-2 clinical trial, both targeting progressing lung cancers.

In 2020, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for REQORSA for non-small cell lung cancer (NSCLC) in combination therapy with Tagrisso (osimertinib) for late-stage patients with EFGR mutations whose tumors progressed after treatment with Tagrisso. In 2021, the FDA granted Fast Track Designation for REQORSA for NSCLC in combination therapy with Keytruda (pembrolizumab) for late-stage patients whose disease progressed after treatment with Keytruda.

The ONCOPREX Nanoparticle Delivery System is designed to deliver tumor suppressor genes, which are encapsulated in lipid nanoparticles. The nanoparticles are then administered intravenously and taken up by tumor cells where the encapsulated gene is translated to express proteins that are missing or depleted in cancer cells. Genprex has treated more than 50 NSCLC patients in clinical trials with REQORSA, the Company’s lead drug candidate that uses the ONCOPREX Nanoparticle Delivery System to deliver the TUSC2 gene.

A Phase 1 clinical trial showed that systemic, intravenous therapy using the ONCOPREX Nanoparticle Delivery System was shown to selectively and preferentially target tumor cells, resulting in clinically significant anticancer activity. The nanoparticles are non-immunogenic, allowing repetitive therapeutic dosing and providing extended half-life in the circulation.

1Cancers 2022, 14(2), 361; View Source