On December 21, 2021 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 Ms. Belen Toledo MSc., from the laboratory of Professor Macarena Perán Ph.D., at the University of Jaén, Spain, recently completed an important experimental thesis on the effects of proenzyme therapy and the impact on the tumor microenvironment, which is key to the development, invasion, metastatic spread, and recurrence of solid tumors (Press release, Propanc, DEC 21, 2021, View Source [SID1234597536]). Ms. Toledo also reconfirmed proenzymes kill cancer stem cells (CSCs). This research is part of the "Proenzymes Optimization Project 1" (POP1) Joint Research and Drug Discovery Program at the Universities of Jaén and Granada, Spain, designed to produce synthetic recombinant, commercial scale quantities of the two proenzymes, trypsinogen and chymotrypsinogen.

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 encouraging results demonstrates that proenzymes have a specific effect on tumor cells and CSCs, but also effects other tumor elements in the tumor microenvironment. However, the most significant conclusion from Ms. Toledo is that the proenzymes also caused a reversal of the malignant tumor phenotype, which was, "most unexpected, very exciting and powerfully conclusive." The process that causes a reversal of the tumor phenotype is called differentiation, which is fundamentally how proenzymes exert anti-tumor, anti-cancer and anti-metastatic effects. Therefore, proenzyme treatment, also known as differentiation therapy, exerts these effects on malignant cells, but leaves healthy cells alone.

"The tumor microenvironment displays certain characteristics common to all solid tumors. Proenzymes normalize this tumor microenvironment," said Dr. Julian Kenyon Mb., ChB., M.D., Propanc’s Chief Scientific Officer. "Therefore, the process of cell differentiation induced by the proenzymes will be applicable to all cancers from solid tumors, as well as sarcomas. This is truly a remarkable finding and may be the key to unlocking the uncontrolled spread of malignant tumors, the main cause of patient death for cancer sufferers. As a result of these findings, I believe there is an urgency in advancing our lead product candidate, PRP, into clinical trials."

The POP1 program is designed to produce a backup clinical compound to the Company’s lead product candidate, PRP. The objective is to produce large quantities of trypsinogen and chymotrypsinogen for commercial use that exhibits minimal variation between lots and without sourcing the proenzymes from animals. Propanc is undertaking the challenging research project in collaboration with the Universities of Jaén and Granada, led by research scientists Mr. Aitor González MSc. and Ms. Toledo, supported by Profs. Perán and Juan Antonio Marchal, M.D., representing the Universities respectively, and Dr. Kenyon.

On December 21, 2021 CStone Pharmaceuticals (the "Company" or "CStone") reported that the National Medical Products Administration ("NMPA") of China has approved the new drug application ("NDA") of anti-PD-L1 monoclonal antibody Cejemly (sugemalimab) in combination with chemotherapy for treatment-naïve metastatic (stage IV) non-small cell lung cancer ("non-small cell lung caner" or "NSCLC") patients (Press release, CStone Pharmaceauticals, DEC 21, 2021, View Source [SID1234597560]).

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!

Key Highlights

Anti-PD-L1 monoclonal antibody Cejemly approved in combination with pemetrexed and carboplatin as first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations; and in combination with paclitaxel and carboplatin as first-line treatment of patients with metastatic squamous NSCLC.
It is the first anti-PD-L1 plus chemotherapy approved for the first-line treatment of metastatic non-squamous and squamous NSCLC patients worldwide.
The NDA of Cejemly in stage III NSCLC is under regulatory review, and the product has the potential to provide an anti-PD-L1 monoclonal antibody option for both stage III and stage IV non-small cell lung cancer patents in the future.
Cejemly is CStone’s third new drug approval in China in 2021, following two first-in-class precision medicines GAVRETO and AYVAKIT.
Globally, the incidence of lung cancer continues to rise, and it is still the leading cause of cancer death worldwide, with huge unmet medical needs. According to statistics, there were 2.21 million new lung cancer cases worldwide in 2020. NSCLC accounts for about 85% of all lung cancer cases, and about 66% of patients are diagnosed with stage III/IV NSCLC. According to IQVIA’s Global Oncology Trends, the size of global oncology drug market is estimated to reach US$269 billion by 2025, of which immuno-oncology drugs will contribute about 20%.

Dr. Frank Jiang, Chairman and CEO of CStone, said: "Cejemly is our third approved new drug in China this year. This further demonstrates CStone’s ability and track record in developing and commercializing high-quality new drugs. As a drug supported by China’s national science innovation program, Cejemly is a globally leading anti-PD-L1 monoclonal antibody. We will work closely with Pfizer to leverage resources and advantages of both sides to accelerate commercialization so that more Chinese patients can benefit from this innovative therapy soon."

Professor Caicun Zhou, Principal Investigator of the GEMSTONE-302 registrational phase III clinical study of Cejemly and Director of the Department of Oncology, Shanghai Pulmonary Hospital, said, "The latest data show that Cejemly plus chemotherapy further prolonged progression-free survival ("PFS") of treatment-naïve patients with stage IV NSCLC. Compared with chemotherapy alone, Cejemly plus chemotherapy demonstrated durable survival benefits with lower toxicity and immunogenicity risks. With a unique dual mechanism of action, Cejemly mobilizes both T cells and macrophages to destroy tumor cells. Therefore, Cejemly is expected to reshape the landscape of lung cancer treatment."

Dr. Jason Yang, Chief Medical Officer of CStone, said, "We are thrilled that Cejemly has been approved in Mainland China. It took only four years for Cejemly to obtain the first NDA approval in lung cancer from the initiation of the phase I clinical trial in humans. It comprehensively showcased CStone’s robust clinical strategy, innovative trial design and rapid execution, while once again demonstrating the ‘CStone Speed’. We will continue to work with our partner to pursue regulatory discussions for Cejemly on the NDAs of stage III and stage IV NSCLC with regulators in multiple countries and regions, including the U.S. Food and Drug Administration, and bring this innovative immunotherapy to more lung cancer patients soon. We will also continue to advance the registrational studies of Cejemly in esophageal squamous cell carcinoma, gastric cancer, relapsed/refractory extranodal natural killer/T-cell lymphoma, to benefit more cancer patients."

The NMPA approval is based on the positive data of GEMSTONE-302 study, a multi-center, randomized, double-blind, phase III study that evaluated the efficacy and safety of Cejemly or placebo in combination with chemotherapy in first-line stage IV NSCLC patients. Compared with placebo plus chemotherapy, Cejemly plus chemotherapy lowered the risk of disease progression or death by 52%, significantly prolonged the patients’ PFS and an encouraging trend in overall survival ("OS") was observed. The clinical benefit was irrespective of NSCLC pathologies and PD-L1 expression levels. Cejemly has a well-tolerated safety profile, and no new safety signals were found.

Apart from the approved indication, the NMPA accepted the NDA of Cejemly as consolidation therapy in patients with unresectable stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy in September 2021. The product has the potential to become an anti-PD-L1 monoclonal antibody approved to cover stage III and stage IV NSCLC in all-comer settings.

About Cejemly (sugemalimab)

The potential best-in-class anti-PD-L1 monoclonal antibody Cejemly (sugemalimab) is an investigational anti-PD-L1 monoclonal antibody discovered by CStone. Authorized by the U.S.-based Ligand Corporation, Cejemly is developed by the OmniRat transgenic animal platform, which can generate fully human antibodies in one stop. As a fully human, full-length anti-PD-L1 monoclonal antibody, Cejemly mirrors the natural G-type immunoglobulin 4 (IgG4) human antibody, which reduces the risk of immunogenicity and potential toxicities in patients, a unique advantage over similar drugs.

Currently, the China NMPA has approved the potential best-in-class anti-PD-L1 monoclonal antibody Cejemly in combination with chemotherapy for the treatment of treatment-naïve patients with stage IV NSCLC. In addition, Cejemly is being investigated in a number of ongoing clinical trials, including one Phase II registrational study for lymphoma and four Phase III registrational studies in stage III NSCLC, stage IV NSCLC, gastric cancer, and esophageal cancer, respectively.

CStone formed a strategic collaboration agreement with Pfizer that includes the development and commercialization of Cejemly in mainland China, and a framework to bring additional oncology assets to the Greater China market.

About the GEMSTONE-302 Study

The GEMSTONE-302 study (ClinicalTrials.gov registration number: NCT03789604; drug clinical trial registration number: CTR20181452) is a randomized, double-blind Phase III study, designed to evaluate the efficacy and safety of anti-PD-L1 monoclonal antibody Cejemly combined with chemotherapy as the first-line treatment in treatment-naïve patients with stage IV NSCLC vs. placebo combined with chemotherapy. The primary endpoint of the study was investigator-assessed PFS. Secondary endpoints included OS, BICR-assessed PFS and safety, etc.

In August 2020, the GEMSTONE-302 study met its primary endpoint of significantly prolonged PFS, with the risk of disease progression or death reduced by 50% with Cejemly combined with chemotherapy compared to placebo combined with chemotherapy, as assessed by iDMC at the planned interim analysis. Specific study data were presented in a Proffered Paper Oral Presentation (Late-Breaking Abstract) at the ESMO (Free ESMO Whitepaper) Asia 2020.

In July 2021, the final analysis of PFS from the GEMSTONE-302 study showed that Cejemly in combination with chemotherapy demonstrated further improvement in PFS and the risk of disease progression or death was reduced by 52%, together with a trend of OS benefits. Data were presented in a Mini Oral Presentation (Late-Breaking Abstract) at the IASLC 2021 World Conference on Lung Cancer.

On December 21, 2021 Apollo Endosurgery, Inc. ("Apollo") (NASDAQ: APEN), a global leader in less invasive medical devices for gastrointestinal and bariatric procedures, reported that it has entered into a debt financing agreement with an affiliate of Innovatus Capital Partners, LLC ("Innovatus") to provide Apollo with up to $100 million in term loan financing (Press release, Apollo Endosurgery, DEC 21, 2021, View Source [SID1234597520]).

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!

"We are pleased to partner with a long-term strategic investor such as Innovatus in this transaction," said Chas McKhann, president and CEO. "This new loan facility provides us flexibility to invest in our business and fund our growth initiatives through minimally-dilutive financing. Importantly, with this additional capital source, our management team can focus on unlocking the value in our business through continued execution."

The new term loan reduces Apollo’s cost of capital, extends amortization by an additional 33 months over the prior term loan and decreases debt service cash requirements by nearly $30 million over the next three years.

"Innovatus is excited to work with Apollo and its management team," said Claes Ekstrom, Managing Director. "We believe this transaction enables Apollo to accelerate the adoption of its portfolio of highly differentiated products across a wide range of patient needs."

On December 21, 2021, Apollo entered into a loan and security agreement (the "Loan Agreement") pursuant to which Innovatus has agreed to make certain term loans in the aggregate principal amount of up to $100 million, with the first $35 million tranche (Term A Tranche) to be funded at closing and used to retire Apollo’s existing term debt facility with SLR Capital Partners.

Apollo will be eligible to draw on additional tranches commencing June 30, 2022 as follows:
•Term B Tranche of $15 million between July 1, 2023 and December 31, 2023, upon achievement of certain revenue milestones;
•Term C Tranche of $25 million between July 1, 2024 and December 31, 2024, upon achievement of certain revenue milestones; and
•Term D Tranche of up to $25 million second between June 30, 2022 and June 30, 2024, for the purposes of financing all or part of any approved acquisition.

Borrowing under the Loan Agreement will bear interest at the greater of the Wall Street Journal Prime Rate or 3.25%, plus 4.0% (currently, 7.25%). Apollo is entitled to make interest-only payments for 60 months, followed by monthly payments of principal and interest through maturity on the sixth anniversary of the initial funding date.

The Loan Agreement is secured by substantially all of Apollo’s assets.

Prior to December 21, 2025, Innovatus will have the right, but not the obligation, to make a one-time election to convert up to 10% of the outstanding aggregate principal amount of the term Loans into shares of common stock of Apollo. Such shares shall be issued at a price per share equal to $11.50.

Credo 180 acted as sole financial advisor to Apollo on this transaction.

Additional details regarding the financing will be included in a Current Report on Form 8-K, which Apollo will file with the Securities and Exchange Commission within four business days of the date of this press release.

On December 21, 2021 UroGen Pharma Ltd. (Nasdaq: URGN), a biopharmaceutical company dedicated to building and commercializing novel solutions that treat urothelial and specialty cancers, reported that the first patient has received their first dose in its home instillation study of UGN-102 in patients with low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) (Press release, UroGen Pharma, DEC 21, 2021, View Source [SID1234597537]).

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 objective of this Phase 3b study, which aims to enroll up to ten patients across four centers, is to demonstrate whether UGN-102 can be administered at home by a qualified home health professional, avoiding the need for repeated visits to a healthcare setting for instillation.

"The ease of UGN-102 instillation is of great benefit to these patients who are generally older, suffer from multiple comorbidities, and often rely on caregivers to drive them to medical appointments," said Mark Schoenberg, M.D., Chief Medical Officer of UroGen. "Home instillation is especially convenient for the patient and less burdensome for caregivers as they navigate persistent challenges caused by repeated medical appointments. We look forward to demonstrating the versatility of UGN-102 in this study as we prepare to initiate the single-arm, pivotal Phase 3 ENVISION Study of UGN-102 in early 2022."

Patients in the ongoing Phase 3b study will receive six once-weekly intravesical instillations of UGN-102. The initial treatment visit will occur at the investigative site and instillation will be performed by a qualified physician. Treatment visits two to six will take place at the patient’s home and instillation will be performed by a properly trained and qualified home health professional. The primary endpoint of the study is the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, discontinuations from at home study treatment, and clinically significant abnormalities in laboratory tests (hematology, serum chemistry, and urinalysis).

About UGN-102 (mitomycin for intravesical solution)
UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.

About LG-IR-NMIBC
With 80,000 estimated cases of bladder cancer per year, approximately 35,000 are low-grade NMIBC patients comprised of both low-risk (approximately 15,000) and intermediate risk (approximately 20,000). These patients face a future of recurrence and additional surgeries. Recurrence in LG-IR-NMIBC is a pervasive and often underestimated problem. In patients who recur, it is estimated that 68 percent will experience two or more recurrence episodes throughout the course of their disease, a considerably high and frequent rate in contrast to other non-metastatic cancers.

Currently, the only effective primary treatment available is a surgical procedure known as transurethral resection of the bladder (TURBT). The more the procedure is performed, the more it imposes burden and serious risks on patients. Research shows that 25 percent of patients are not appropriate for TURBT due to physical factors such as age and comorbid conditions or an unwillingness to undergo surgery. Major challenges exist with the current standard of care and these patients deserve a new primary, non-surgical treatment option.

On December 21, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company developing ex vivo allogeneic CAR T therapies and in vivo therapies with its ARCUS genome editing platform, reported that it has entered into an agreement with a syndicate of investors led by ACCELR8 to separate its wholly owned Elo Life Systems subsidiary and create an independent food and agriculture business (Press release, Precision Biosciences, DEC 21, 2021, View Source [SID1234597581]).

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 separation of Precision BioSciences and Elo Life Systems was an important 2021 corporate imperative intended to enable operational success for both companies going forward," said Michael Amoroso, Chief Executive Officer of Precision BioSciences. "Elo is now a separate food and agriculture business, with independent financial resources and focused core capabilities to support its essential mission to improve human health and wellness through food. In parallel, this transaction enables Precision to focus exclusively on human therapeutics and leverage the unique attributes of ARCUS to develop a potential new class of off-the-shelf CAR T products for cancer and in vivo gene editing therapies for patients with genetic diseases."

Pursuant to the agreement, Precision BioSciences contributed substantially all assets and liabilities of Elo Life Systems to a new entity in which Precision maintains an equity stake. All employees of Elo, including its management, transitioned to the new company as part of the agreement.