On November 23, 2021 Novocure (NASDAQ: NVCR) reported it will participate in two upcoming investor conferences (Press release, NovoCure, NOV 23, 2021, View Source [SID1234595988]).

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!

William Doyle, Novocure’s Executive Chairman, and Ashley Cordova, Novocure’s Chief Financial Officer, will participate in the 33rd Annual 2021 Piper Sandler Healthcare Conference on November 30, 2021. Mr. Doyle and Ms. Cordova will take part in a fireside chat at 1 p.m. EST, as well as one-on-one meetings with investors throughout the event. A live audio webcast of the presentation can be accessed from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for replay for at least 14 days following the event.

Ms. Cordova will be joined by Pritesh Shah, Novocure’s Chief Commercial Officer, for additional one-on-one meetings with investors as part of the 4th Annual 2021 Evercore ISI HealthCONx Conference on December 2, 2021.

Novocure’s corporate presentation is updated periodically, and the current presentation can be accessed from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations. Novocure has used, and intends to continue to use, its Investor Relations website as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

On November 23, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported that the European Commission (EC) has granted marketing authorization for Trodelvy (sacituzumab govitecan), a first-in-class Trop-2-directed antibody-drug conjugate, as a monotherapy indicated for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for advanced disease (Press release, Gilead Sciences, NOV 23, 2021, View Source [SID1234595986]).

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 metastatic stage of TNBC is particularly challenging to treat and until now we have urgently needed new treatment options for people in Europe living with this condition," said Dr Véronique Diéras, Senior Medical Oncologist Head, Breast Cancer Group, Department of Medical Oncology, Centre Eugène Marquis, Rennes, France. "Today’s approval including second-line metastatic TNBC is significant for the community as it’s another important step forward in helping women with this disease live longer."

TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. It is more frequently diagnosed in younger and premenopausal women and is more prevalent in Black and Hispanic women. The five-year survival rate for this sub-type of breast cancer is 12%, compared with 28% for other breast cancer types, and these poor outcomes are often coupled with a significant decrease in quality of life, especially in relapsed/refractory disease.

"At Gilead, we push boundaries to deliver transformative science and novel treatment options that address urgent medical needs," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "We understand how difficult metastatic TNBC is to treat and we’re proud that Trodelvy can now offer a second-line treatment option with the potential to bring longer life to people living with this aggressive disease."

The EC’s decision is supported by results from the Phase 3 ASCENT study, where Trodelvy reduced the risk of death by 49% and improved median overall survival to 11.8 months versus 6.9 months with physician’s choice of chemotherapy (HR: 0.51; 95% CI: 0.41-0.62; p<0.0001). These data also showed a statistically significant and clinically meaningful 57% reduction in the risk of death or disease worsening and improved median progression free survival (PFS) to 4.8 months from 1.7 months seen with physician’s choice of chemotherapy alone among all randomized patients, which included those with and without brain metastases (HR: 0.43; 95% CI: 0.35-0.54; p<0.0001). The most common Grade 3 or higher adverse reactions were neutropenia (49.5%), leukopenia (12.0%), diarrhea (10.7%), anemia (10.1%), febrile neutropenia (6.6%), fatigue (5.2%), hypophosphatemia (5.2%), nausea (4.1%) and vomiting (3.0%).8 The Trodelvy U.S. Prescribing Information has a BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea; see below for Important Safety Information.

In addition to this approval, Trodelvy is approved in Australia, Canada, Great Britain, Switzerland, and the United States in metastatic TNBC. Regulatory review is also underway in Singapore and China with applications submitted by Everest Medicines. Trodelvy was also recently included in the updated ESMO (Free ESMO Whitepaper) Clinical Practice Guidelines as a preferred treatment option for metastatic TNBC after taxanes.

About the ASCENT Study

The ASCENT study is a global, open-label, randomized Phase 3 study that enrolled more than 500 patients across 230 study locations. The study evaluated the efficacy and safety of Trodelvy compared with a single-agent chemotherapy of the physician’s choice in patients with unresectable, locally advanced or metastatic TNBC who had received at least two prior systemic treatments. Patients were randomly allocated to receive either Trodelvy or a chemotherapy chosen by the patient’s treating physician. The primary endpoint was progression-free survival (PFS, as determined by blinded independent central review) in patients without brain metastases. Secondary endpoints included: PFS for full study population or intention-to-treat (ITT) population, overall survival in both the ITT population and in the subgroup without brain metastasis, independently determined objective response rate, duration of response, time to onset of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), quality of life and safety. More information about ASCENT is available at View Source

About Triple-Negative Breast Cancer (TNBC)

TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. TNBC is diagnosed more frequently in younger and premenopausal women and is more prevalent in Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited human epidermal growth factor receptor 2 (HER2). Due to the nature of TNBC, effective treatment options are extremely limited compared with other breast cancer types. TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of metastatic breast cancer.

About Trodelvy

Trodelvy is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein overexpressed in multiple types of epithelial tumors, including metastatic TNBC and metastatic urothelial cancer (UC), where high expression is associated with poor survival and relapse. Trodelvy is approved in second-line metastatic TNBC in multiple countries worldwide, including Australia, Canada, Great Britain, the European Union, Switzerland and the United States. Trodelvy is also approved for use in metastatic UC in the United States. Trodelvy continues to be developed for potential use in other TNBC and metastatic UC populations and is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.

Important Safety Information for Trodelvy as Included in the U.S. Prescribing Information for Trodelvy

Recommendations for the use of Trodelvy in the EU (including final safety information for prescribers) have been assessed as part of the Marketing Authorization Application and are detailed in full in the EU SmPC.

Recommendations for the use of Trodelvy in other countries outside of the U.S. are subject to assessment by the relevant local regulatory authority as part of the registration/marketing authorization process. Once approved recommendations are detailed in the local prescribing information.

WARNING: NEUTROPENIA AND DIARRHEA

Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS

Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 61% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 7%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever.

Diarrhea: Diarrhea occurred in 65% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of patients. One patient had intestinal perforation following diarrhea. Neutropenic colitis occurred in 0.5% of patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic reactions was 0.3%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions.

Nausea and Vomiting: Nausea occurred in 66% of all patients treated with Trodelvy and Grade 3 nausea occurred in 4% of these patients. Vomiting occurred in 39% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 67% in patients homozygous for the UGT1A1*28, 46% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 25% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 11% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were fatigue, neutropenia, diarrhea, nausea, alopecia, anemia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes.

In the TROPHY study (IMMU-132-06), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, neutropenia, nausea, any infection, alopecia, anemia, decreased appetite, constipation, vomiting, abdominal pain, and rash. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy.

On November 23, 2021 Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported a clinical update for the Company’s Phase 1b Expansion trial evaluating APVO436 in the treatment of acute myeloid leukemia (AML) (Press release, Aptevo Therapeutics, NOV 23, 2021, https://aptevotherapeutics.gcs-web.com/news-releases/news-release-details/aptevo-therapeutics-reports-first-complete-remission-providing [SID1234595985]). Preliminary data observed to date includes one complete remission.

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!

A high-risk AML patient treated in Cohort 1 with a combination of chemotherapy plus APVO436 achieved a complete remission (CR) after one cycle of therapy. The chemotherapy regimen included the standard leukemia drugs Mitoxantrone, Etoposide, and Cytarabine. The patient tolerated treatment without evidence of overt toxicity.

The overarching goal of the Phase 1b expansion phase study is to determine if APVO436 treatments can improve the quality of remission in high-risk AML patients by reducing the residual chemotherapy-resistant measurable residual disease (MRD) burden. The quality of remission will be assessed using state-of-the art multiparameter flow cytometry methods for quantitative MRD assessment in a centralized laboratory.

MRD, previously known as minimal residual disease, in AML refers to leukemia cells that are present at very low numbers but can be detected using highly sensitive flow cytometric or genomic methods. A recent systematic review of the clinical significance of MRD in over 10,000 AML patients has demonstrated that achievement of MRD negativity is associated with superior leukemia-free survival and overall survival. Therefore, MRD status has emerged as an attractive and clinically meaningful end point that may allow for accelerated evaluation of novel therapies in AML (reference: Short et al., Association of Measurable Residual Disease with Survival Outcomes in Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. JAMA Oncol. 2020 Dec 1;6(12):1890-1899. Click here to view the publication: View Source

Aptevo believes that APVO436 has the potential to help AML patients achieve complete remissions without MRD and thereby reduce their risk of leukemic relapses. Aptevo also believes that the use of APVO436 for targeting MRD in AML may be associated with a very low risk of cytokine release syndrome (CRS) as well as an increased likelihood of responses as both CRS as well as responses are inversely correlated with the leukemia burden of the patients. If successful, deepening the remission to an MRD-negative remission using this strategy could translate into an improved overall survival in AML.

The Company recently published information about the compound’s favorable safety profile, characterized by a low incidence of CRS, and promising single agent activity of APVO436 in two back-to-back peer-reviewed publications in the prestigious oncology journal Cancers (Basel):

1. Uckun, F.M.; Lin, T.L.; Mims, A.; Patel, P.; Lee, C.; Shahidzadeh, A.; Shami, P.; Cull, E.; Cogle, C.R.; Watts, J. A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplasia. Cancers (Basel) 2021, 13, Aug 15;13(16):4113. Click here to view the publication: View Source

2. Uckun FM, Watts J, Mims AS, Patel P, Wang E, Shami PJ, Cull E, Lee C, Cogle CR, Lin TL. Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436. Cancers (Basel) 2021; 13(21):5287. Click here to view the publication: View Source

About APVO436
Overexpression of CD123 is the hallmark of many forms of leukemia. Aptevo’s lead proprietary drug candidate, APVO436 is a bispecific CD3xCD123 ADAPTIR that is designed to redirect the immune system of the patient to destroy leukemia cells expressing the target CD123 molecule on their surface. This antibody-like recombinant protein therapeutic is designed to engage both leukemia cells and T-cells of the immune system and bring them closely together to trigger the destruction of leukemia cells. APVO436 has been engineered using Aptevo’s proprietary and enabling bioengineering methods and is designed to reduce the likelihood and severity of CRS. APVO436 has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act.

On November 23, 2021 Pacira BioSciences, Inc. (NASDAQ: PCRX) reported that it will participate in an analyst-led fireside chat at the Piper Sandler 33rd Annual Virtual Healthcare Conference at 9:30 AM ET on Tuesday, November 30, 2021 (Press release, Pacira Pharmaceuticals, NOV 23, 2021, View Source [SID1234595984]). Live audio of the event can be accessed by visiting the "Events" page of the company’s website at investor.pacira.com. A replay of the webcast will also be available for two weeks following the event.

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!

On November 23, 2021 Oncotelic Therapeutics, Inc. ("Oncotelic" or the "Company") (OTCQB:OTLC) reported financial results for the third quarter ended September 30, 2021 ("Q3 2021"), as well as an update on its product and therapeutic development initiatives and other corporate updates (Press release, Oncotelic, NOV 23, 2021, View Source [SID1234595983]).

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!

Q3 2021 compared to Q3 2020 Financial Results Overview –

Total operating expenses for Q3 2021 increased to $1.8 million from $1.6 million in Q3 2020, due to a $0.3 million decrease in R&D expense and a $0.5 million increase in general & administrative expenses. The decrease in R&D expense was due to lower personnel and clinical development costs in Q3, 2021 as compared to that in Q3 2020. The increase in G&A expense was due to higher stock compensation expense of $0.6 million as reduced by lower legal and professional expenses of $0.1 million during Q3 2021 as compared to Q3 2020.

Net loss attributable to common stockholders for Q3 2021 was $1.6 million, or ($0.00) per common share, compared to a net loss of $2.0 million, or ($0.02) per common share, for Q3 2020. The lower net loss per common share was due to the higher weighted average share in 2021 due to the conversion of our preferred shares in Q1 2021.

Subsequent events: In September 2021, the Company secured $1.5 million in debt financing as per the term sheet for the formation of a joint venture with Golden Mountain Partners ("GMP") signed in August 2021; and subsequently an additional $0.5 million in October 2021 as we move towards formalizing the joint venture with GMP. In aggregate, GMP has invested $5.2 million in OT-101. As of this week, there are multiple bids for OT-101, which are being reviewed by the Company and the Board.

Highlights for Q3 2021 and thereafter:

In August 2021 the Company and GMP executed letter of intent and a non-binding term sheet to which the Company and GMP will, subject to shareholder approval, form a joint venture (the "JV") with the objective to develop the Company’s product portfolio. Pursuant to the Term Sheet, the Company will contribute its product portfolio to the JV in consideration for a 35% ownership stake in the JV. The term sheet set forth the issuance by the Company of a convertible note for $1.5 million to GMP to fund the OT-101 clinical trial study close-out. In September 2021, the Company entered into an unsecured convertible note purchase agreement with GMP, pursuant to which the Company issued a convertible promissory note in the aggregate principal amount of $1.5 million, convertible into shares of the Company’s Common Stock. Further, in October 2021, the Company entered into an unsecured convertible note purchase agreement with GMP, pursuant to which the Company issued a convertible promissory note in the aggregate principal amount of $0.5 million, which note is convertible into shares of the Company’s Common Stock.

In September 2021, the Company entered into an exclusive License Agreement (the "Agreement") with Autotelic, Inc. ("Autotelic"), pursuant to which Autotelic granted the Company the exclusive right and license to certain Autotelic Patents and Know-How and a right of first refusal to acquire at least a majority of the outstanding capital stock of Autotelic prior to Autotelic entering into any transaction as defined in the agreement. In exchange for the rights granted to Oncotelic, Autotelic will be entitled to earn the milestone payments of up to $50 million upon achievement of certain financial, development and regulatory milestones and royalties equal to 15% of the net sales of any products that incorporate the Autotelic Patents or Autotelic Know-How.

"We are very encouraged by the progress being made at Oncotelic through the first nine months of 2020," said Amit Shah, CFO of Oncotelic. "We look forward to the completion of our JV so that the OT-101 asset can be fully developed especially in response to the current surge in COVID-19 globally due to the new variants. At the same time, we are leveraging on our previous successes along the 505(b)2 strategy for the development of AL-101 as our lead fast to market drug candidate"

Additional information is included in the Company’s Form 10-Q for the period ended September 30, 2021, filed on November 22, 2021, a copy of which is available free of charge at View Source

Recent Product Development Highlights

AL-101 CNS Program
AL-101 (intranasal apomorphine), 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 CNS effects that will be leverage 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.

Over 60,000 new patients annually being diagnosed with PD in the United States and 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 developed for initiation early 2022. 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 Keytruda, 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 is a first-in-class anti-TGF-β ribonucleic acid ("RNA") therapeutic that has exhibited single agent activity in relapsed/refractory cancer patients in multiple clinical trials. OT-101 has also demonstrated activity against the SARS-CoV-2 virus, the virus that causes COVID-19, and is currently being evaluated in the Company’s C001 clinical trial against hospitalized severe COVID-19.

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 pts
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. This aspect is important as we have identified mutations occurring on ORF-8 of SARS-Cov-2 on the delta variant backbone that is increasing in frequencies and could confer immune evasion properties to the virus.

Artemisinin COVID-19 Program
We have deployed Artemisinin as herbal supplement in India under the name PulmoHeal 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. We look forward to completion of the WHO trial on artesunate against COVID-19 as validation of our ARTI19 clinical trial among 120 pts in India. The larger WHO trial should provide the definitive efficacy data for further development of the drug.