On May 23, 2022 Oncotelic Therapeutics, Inc. ("Oncotelic", "We" or the "Company") (OTCQB:OTLC) reported financial results for the three months ended March 31, 2022 ("Q1 2022") as compared to the three months ended March 31, 2021 ("Q1 2021"), an update on its product and therapeutic development initiatives and other corporate updates (Press release, Oncotelic, MAY 23, 2022, View Source [SID1234614952]). The financial results were based on the Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 23, 2022.
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Highlights for Q1 2022 and thereafter:
As previously reported, on March 31, 2022, we entered into a joint venture, or JV, with Dragon Overseas Capital Ltd. (Dragon Overseas) and GMP Biotechnology Ltd. (GMP Bio). Dragon Overseas and GMP Bio are affiliated with GMP. The intent is to develop and ultimately market OT-101, individually and in combination with other products, along with our JV partners.
Highlights of the transaction include:
Oncotelic to receive up to $50 million on sale of the RPD voucher following marketing approval of OT-101 for diffuse intrinsic pontine glioma, or DIPG.
Dragon Overseas has agreed to invest cash and other assets with a value of approximately $27.6 million for 55% ownership of the JV.
Oncotelic has licensed OT-101 to the JV for a 45% ownership in the JV.
The JV to be headquartered in Hong Kong.
Initial focus on the further development and commercialization of OT-101, including for DIPG as well as pancreatic cancers and glioblastoma.
The JV is planned to be taken into an IPO at a future point in time.
"With the JV transaction, clinical trial cost and payroll cost related to OT-101 has effectively been transferred to the JV, greatly reducing the operational cost of Oncotelic making up listing a strong possibility," commented Amit Shah, CFO.
"This week, we filed the patent application entitled TGF-beta therapeutics for age disease codifying the treatment of age-related disease such as cancers and infectious diseases as intervention on aging.," said Dr. Trieu, CEO and Chairman "we see a robust future for Oncotelic and the JV as the leaders in this new era of medicine".
When compared between Q1 2022 and Q1 2021, our research and development ("R&D") expenses decreased by approximately $1.0 million. The lower R&D expenses were primarily related to lower clinical trial activity in Q1 2022 as compared to Q1 2021 of approximately $0.9 million and approximately $0.1 million of other operational costs.
When compared between Q1 2022 and Q1 2021, our general and administrative ("G&A") expenses increased by approximately $3.3 million. This was primarily due to the increase of approximately $3.2 million in non-cash stock compensation expense, incurred in connection with issuance of new warrants of approximately $2.9 million and approximately $0.3 million on stock options. Excluding the non-cash stock compensation expense recorded during Q1 2022, our G&A expenses was almost the same as in Q1 2021.
We recorded interest expense, including amortization of debt costs, of approximately $0.3 million for Q1 2022 in connection with debt raised from various convertible notes, including the JH Darbie Financing, as compared to $0.5 million for Q1 2021, due to debt raised from convertible notes in 2021 and the JH Darbie Financing.
During Q1 2022, we recorded a change in the value of the derivative of $0.2 million. We recorded approximately $0.5 million change in value of the derivatives on conversion of the debt to liabilities on the convertible notes issued to our CEO and a bridge investor (collectively, the "Convertible Notes").
During Q1 2022, we recorded a loss on extinguishment of debt of approximately $0.3 million on our JH Darbie Financing, upon granting approximately 33 million warrants to our investors. Correspondingly, we recorded a loss on conversion of debt of $28 thousand million during Q1 2021.
Recent Product Development Highlights
AL-101 CNS Program
AL-101 (intranasal apomorphine) – We had acquired AL-101 in September 2021. AL-101 is our lead fast-to-market 505(b)2 regulatory pathway drug candidate for Parkinson Disease ("PD") and Erectile Dysfunction ("ED"), especially phosphodiesterase 5 ("PDE5") non-responders. Oncotelic also plans to develop AL-101 as a new class of drug against Female Sexual Dysfunction ("FSD"), including Hypoactive Sexual Desire Disorder ("HSDD"). Through targeting the dopamine receptors in the brain AL-101 has multiple central nervous system effects that will be leveraged in its development – mirroring the successes we have had previously with Abraxane and Cynviloq via the 505(b)2 pathway. AL-101 has shown a favorable safety and efficacy profile and is phase 3 ready with six clinical trials completed and over 200 patients (2,200 doses) treated.
With over 60,000 new patients annually being diagnosed with PD in the United States. Currently there are over 1 million patients in the US and expected to increase to over 1.2 million by 2030. In addition, approximately 10 million suffer from this disease globally. View Source As reported by Pharmaceutical Technology by GlobalData Healthcare on May 26, 2020, KYNMOBI (apomorphine HCI) sublingual film was approved through the 505(b)2 pathway for acute, intermittent treatment of OFF episodes in patients with PD. KYNMOBI dissolves under the tongue. Per GlobalData Healthcare, KYNMOBI is expected to generate $219 million annually. View Source We anticipate AL-101 to be a superior product based on rapid and preferential accumulation in the brain.
ED is the most prevalent male sexual disorder globally. The percentages of men affected by ED are as follows: 14.3-70% of men aged 60 years, 6.7-48% of men aged 70 years, and 38% of men aged 80 years (Geerkens MJM et al. (2019). Eur Urol Focus. pii: S2405-4569(19)30079-3).
FSD is a prevalent problem, afflicting approximately 40% of women and there are few available treatment options. In June 2019, the U.S. Food and Drug Administration approved Vyleesi (bremelanotide) to treat acquired, generalized HSDD in premenopausal women. Currently, this is the only available drug treatment. Vyleesi has essentially replaced the only other drug for HSDD – however, it has a long list of drug-drug interactions, including commonly used antidepressants, such as fluoxetine and sertraline. In addition, it has a black box warning regarding its use with alcohol, a combination that has been associated with hypotension and syncopal episodes. Therefore, there is an urgent need for an effective therapy against FSD and HSDD.
OT-101/PD-1 Oncology Program
The OT-101/PD-1 program is designed to assess the impact of OT-101 across multiple cancer indications, where local tumoral secretion of transforming growth factor-beta ("TGF-β") suppressed the clinical activity of checkpoint inhibitors, CAR-T, and vaccines. Multiple phase 2 trials combination of OT-101, with a PD-1 inhibitor, in collaboration with large pharmaceutical company, and leading KOLs around the world, are being planned and developed. These trials span mesothelioma, glioblastoma, lung, and colorectal cancers where AI driven transcriptome analyses will be used to derive the predictive and prognostic biomarker for TGF-β therapeutics, including OT-101.
TGF- β promotes immune evasion. The different components surrounding a tumor are collectively known as the tumor microenvironment (TME). The TGF-β signaling pathway is activated in the TME and the tumor, leading to alteration in the composition of the TME that favors tumor growth and aggressiveness. A major component of the TME, called Cancer-Associated Fibroblasts. help the tumor grow and escape destruction by the host immune system. As such even if an immune cell is sitting next to the tumor cells, it would not do anything because the tumor is making so much TGF, essentially cloaking the tumors. OT-101 inhibits the making TGF- β protein.
A PD-1 inhibitor, such as pembroluzimab, is not chemotherapy or radiation therapy – it is an immunotherapy and it works with our immune system to help fight cancer. Immunotherapy is spectacularly effective. These agents mobilize the immune system to attack the tumor and achieve cure (not just slowing down of the tumor/remission). However, it will work in only about 10% of patients. The rest have too much TGF- β for PD-1 immunotherapy to be effective. Knocking down TGF with OT-101 should improve the cure rate above the 10%. We are hoping that cure rate can reach 100% in the future.
OT-101/IL-2 Oncology Program
Our OT-101/IL-2 combination trial (the "Trial"), has now successfully completed the safety evaluation of its safety cohort, allowing for further expansion of its clinical program into phase 2 and higher doses.
The Trial – A Multi-center, Open label, Phase Ib clinical study to evaluate the safety, tolerance, and efficacy of TASO-001 ("OT-101"), a TGF-β targeting anti-sense oligonucleotide, in combination with recombinant interleukin-2 (Aldesleukin, "IL-2"), in patients with advanced or metastatic solid tumor cancer. ClinicalTrials.gov Identifier: NCT04862767. The Trial is being conducted by Autotelic BIO, a partner of Oncotelic on the OT-101/IL-2 combination.
In the safety cohort treated during the Trial, the standard dosage of 140mg/m2 of OT-101was well tolerated in combination with IL-2, which has allowed for ongoing dose escalation to 190 mg/m2. The 140 mg/m2 dose was shown to be the optimal dose for OT-101 in a prior trial targeting pancreatic cancer, melanoma, and colorectal cancer ("P001"). In the P001 trial, the maximum tolerated dose was not reached even at 330 mg/m2. Therefore, the Company believes that increasing the dose above 140 mg/m2 should further enhance the clinical activity of OT-101.
OT-101 COVID-19 program
On October 18, the data lock of the Study Data and Analysis Data Models (SDTMs & ADaMS Databases) were generated for the Company’s C001 trial for COVID-19. The trial compares OT-101 plus standard of care ("SOC") versus Placebo plus SOC, the SOC which includes dexamethasone (N= 32 pts at 2:1 randomization ratio). Dexamethasone is the only known drug to improve outcome for severe COVID-19. The top line data as previously disclosedare:
Safety endpoints met. OT-101 as a TGF-β inhibitor was safe to administer to COVID-19 patients including severe/critical COVID-19 patients.
Efficacy signals were obtained. End of treatment- Day 7-mortality for the entire study population was 4.5% OT-101 versus 20% Placebo.
Incidence of >96% viral load knockdown on End of Treatment- Day 7- was 89% for OT-101 versus 67% for placebo.
Overall survival improved significantly improved from 4 day for placebo to 14 day OT-101 among critically ill COVID-19 patients.
The data form the basis for us to further develop this as a drug to treat severe respiratory viral infections including flu and COVID. Both tumor cells and the SARS-CovCoV-2 viruses induce TGF-β as part of their immune evasion mechanism. Consequently, inhibiting TGF-β by OT-101 is expected to impact both cancer and COVID. By targeting the host protein, OT-101 is expected to work against multiple respiratory viruses agnostic of the emerging variants, unlike traditional antiviral drugs and vaccines.
Artemisinin COVID-19 Program
We deployed Artemisinin as herbal supplement in India under the name PulmoHealTM together with Chopra Foundation and Heart Care Foundation of India (HCFI) and Parmarth Niketan Ashram to combat COVID during the deadly surge in COVID-19 in summer of 2021 as a humanitarian effort. As we build our patent portfolio around Artemisinin and its analogs for COVID-19 and other respiratory viral infections we are positioning Artemisinin and its analog artesunate as pharmaceutics.