On February 15, 2022 Palatin Technologies, Inc. (NYSE American: PTN), a biopharmaceutical company developing first-in-class medicines based on molecules that modulate the activity of the melanocortin and natriuretic peptide receptor systems, reported results for its fiscal second quarter ended December 31, 2021 (Press release, Palatin Technologies, FEB 15, 2022, View Source [SID1234608116]).

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"We are pleased to have initiated a Phase 3 pivotal study of PL9643 in patients with dry eye disease and expect topline results in the second half of calendar year 2022," stated Carl Spana, Ph.D., President and CEO of Palatin. "Regarding Vyleesi, our focused plan continues to show positive trends for our targeted value metrics related to commercial insurance reimbursement and net revenue per dispensed prescription."

Dr. Spana further commented, "Our strong cash position of approximately $47 million at December 31, 2021, provides us with a sufficient operating cash runway through at least March 2023, including advancing our novel and differentiating melanocortin-based programs, including topline data readouts in the second half of calendar year 2022 for our Phase 3 pivotal study of PL9643 in dry eye disease and for our Phase 2 clinical trial of PL8177 in ulcerative colitis."

Second Quarter Ended Fiscal Year 2022 Financial Highlights

Net loss for the quarter ended December 31, 2021, was $8.7 million, or $0.04 per common share, compared to a net loss of $10.0 million, or $0.04 per common share, for the same period in 2020.

As of December 31, 2021, the Company had cash and investments of $47.3 million, compared to $53.4 million as of September 30, 2021, and $60.1 million as of June 30, 2021, and no debt.

Business Highlights and Updates

Anti-Inflammatory / Autoimmune Programs

PL9643 melanocortin agonist for the treatment of dry eye disease (DED):

Initiated pivotal Phase 3 clinical program in DED patients in December 2021. Topline data readout expected in the second half of calendar year 2022.

■PL8177 melanocortin agonist for the treatment of ulcerative colitis (UC):

Presented the positive effects of PL8177 on treating UC in an animal disease model, including genomic data characterizing the anti-inflammatory effects of melanocortin agonists at the 2022 Crohn’s and Colitis Congress.

A Phase 2 oral formulation study of PL8177 in UC is currently scheduled to start in the first half of calendar year 2022. Topline data readout currently expected in the second half of calendar year 2022.

Presented the protective effects of PL8331 and PL9654 in mouse models of retinopathy, at the 2021 Annual Meeting of the American Society of Retina Specialists (ASRS). Awarded "Top Ten Poster" Designation.

Vyleesi (bremelanotide injection) / Hypoactive Sexual Desire Disorder (HSDD): Goal of the Vyleesi program is to demonstrate product value in the marketplace with an objective of re-licensing the U.S. rights to a committed women’s healthcare company.

For the quarter ended December 31, 2021:

Gross product sales decreased 18% and net product revenue increased 144%, over the comparable quarter in 2020.

Gross product sales decreased 46% and net product revenue decreased 55%, over the prior quarter ended September 30, 2021. This decrease was primarily a result of the pharmacy distributors minimizing their end of year inventory levels.

Second Fiscal Quarter Ended December 31, 2021 Financial Results

Revenue

Total revenue consists of gross product sales of Vyleesi, net of allowances and accruals, and license and contract revenue.

Vyleesi gross product sales to pharmacy distributors for the quarter ended December 31, 2021, amounted to $0.8 million, with net product revenue of $72,140, compared to gross product sales of $0.9 million, with negative net product revenue of $(163,971), for the comparable quarter in 2020. Gross product sales decreased 18% and net product revenue increased 144%, over the comparable quarter in 2020.

For the quarter ended December 31, 2021, Palatin recognized $250,000 in license and contract revenue pursuant to its license agreement with Fosun Pharma. There were no license revenues recognized during the comparable quarter in 2020.

Operating Expenses

Total operating expenses for the quarter ended December 31, 2021, were $8.8 million, compared to $9.1 million for the comparable quarter in 2020.

The decrease in operating expenses was the result of decreased commercial expenses related to Vyleesi, offset by increased research and development expenses primarily related to the advancement of PL9643 into a pivotal phase 3 clinical trial.

Other (Expenses) / Income

Total other expenses, net, consist mainly of unrealized foreign currency losses of $234,078 and $745,002, respectively, for the quarters ended December 31, 2021 and 2020.

Cash Flows

Palatin’s net cash used in operations for the quarter ended December 31, 2021, was $6.3 million, compared to net cash used in operations of $14.4 million for the same period in 2020. The decrease is mainly due to a one-time negotiated payment of approximately $7 million in the quarter ended December 31, 2020 related to inventory purchase commitments of Vyleesi, assumed as part of our Termination Agreement with AMAG Pharmaceuticals, which included $16.3 million of payments by AMAG to Palatin.

Net Loss

Palatin’s net loss for the quarter ended December 31, 2021, was $8.7 million, or $0.04 per basic and diluted common share compared to a net loss of $10.0 million, or $0.04 per basic and diluted common share, for the same period in 2020.

The difference between the quarter ended December 31, 2021, and the quarter ended December 31, 2020, was due to the combination of the increase in revenue recognized, the decrease in operating expenses and the decrease in unrealized foreign currency losses recorded for the quarter ended December 31, 2021, compared to the same period in 2020.

Total prescriptions dispensed were flat compared to the same period in 2020, and the prior quarter ended September 30, 2021.

Commercial insurance reimbursement and net revenue per prescription dispensed increased over the comparable quarter in 2020, and the prior quarter ended September 30, 2021.

Patients and healthcare providers can learn more about HSDD and Vyleesi at www.vyleesi.com and www.vyleesipro.com

Research and Development Infrastructure: Continued to strengthen the R&D department with key appointments who have demonstrated a high-level of expertise in their fields to support the advancement of our programs.

Cash Position

As of December 31, 2021, Palatin’s cash and cash equivalents were $47.3 million with $0.6 million of accounts receivable, compared to cash and cash equivalents of $53.4 million with $0.9 million of accounts receivable as of September 30, 2021 and $60.1 million of cash and cash equivalents with $1.6 million of accounts receivable as of June 30, 2021.

Based on its current operating plan, Palatin believes that existing cash and cash equivalents will be sufficient to fund currently anticipated operating expenses through at least March 31, 2023.

Conference Call / Webcast

Palatin will host a conference call and audio webcast on February 15, 2022 at 11:00 a.m. Eastern Time to discuss the quarter ended December 31, 2021 results of operations in greater detail and provide an update on corporate developments. Individuals interested in listening to the conference call live can dial 1-800-289-0720 (US/Canada) or 1-856-344-9142 (International), conference ID 8966903. The audio webcast and replay can be accessed by logging on to the "Investor/Webcasts" section of Palatin’s website at View Source A telephone and audio webcast replay will be available one hour after the completion of the call. To access the telephone replay, dial 1-888-203-1112 (US/Canada) or 1-719-457-0820 (International), passcode 8966903. The webcast and telephone replay will be available through February 22, 2022.

About Melanocortin Receptor Agonists and Inflammation

The melanocortin receptor ("MCr") system has effects on inflammation, immune system responses, metabolism, food intake, and sexual function. There are five melanocortin receptors, MC1r through MC5r. Modulation of these receptors, through use of receptor-specific agonists, which activate receptor function, or receptor-specific antagonists, which block receptor function, can have medically significant pharmacological effects.

Many tissues and immune cells located in the eye (and other places, for example the gut and kidney) express melanocortin receptors, empowering our opportunity to directly activate natural pathways to resolve disease inflammation.

On February 15, 2022 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing novel cancer therapies and infectious disease vaccines based on the Company’s proprietary Versamune and Infectimune T-cell activating technologies, reported the initiation of an Investigator-Initiated Trial (ITT), MC200710, for PDS0101 alone or in combination with the checkpoint inhibitor, KEYTRUDA, in patients with HPV-associated oropharyngeal cancer (HPV(+)OPSCC) at high risk of recurrence (Press release, PDS Biotechnology, FEB 15, 2022, View Source [SID1234608115]). The trial is being led by Drs. David Routman, Katharine Price, Kathryn Van Abel, and Ashish Chintakuntlawar of Mayo Clinic, a nationally and internationally recognized center of excellence for the treatment of head and neck cancers.

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HPV(+)OPSCC is now the most common type of head and neck cancer and has been increasing significantly in recent years. Oropharyngeal cancer is a disease in which cancer cells form in the tonsil tissues of the back (base of tongue) and side (palatine tonsils) of the throat. According to the National Cancer Institute, smoking or being infected with the human papillomavirus (HPV), especially HPV16, can increase the risk of oropharyngeal cancer. The American Cancer Society estimates there are over 54,000 new cases of oral and oropharyngeal cancer and over 11,000 related deaths in the United States, annually.

"We are excited to have a team of doctors at Mayo Clinic conducting a trial to study our novel Versamune-based T cell immunotherapy platform and lead asset, PDS0101 in earlier-stage disease," commented Dr. Lauren Wood, Chief Medical Officer of PDS Biotech. "This upcoming trial not only broadens our addressable patient population of those affected by the increasing incidence of HPV(+)OPSCC, but also allows us to better understand the activity of PDS0101 alone or in combination with KEYTRUDA in earlier stages of disease."

The study treatment will be administered before patients proceed to transoral robotic surgery (TORS) with curative intent. Treatment in this setting is referred to as neoadjuvant treatment. PDS0101 has been shown to induce killer T-cells that target and kill HPV-positive cancers, either alone or in combination with checkpoint inhibitors in preclinical studies, and in combination in clinical studies of patients with advanced recurrent/metastatic HPV-associated cancers. This study will explore whether PDS0101 with or without checkpoint inhibition may increase HPV-specific anti-tumor responses, potentially resulting in tumor shrinkage, pathologic regression, and decreases in circulating tumor DNA (ctDNA).

On February 15, 2022 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported program updates across its pipeline and anticipated 2022 highlights (Press release, Monopar Therapeutics, FEB 15, 2022, View Source [SID1234608114]).

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Program Developments

Validive – International Phase 2b/3 VOICE Clinical Trial, Actively Recruiting

Severe oral mucositis (SOM) is a painful and debilitating ulceration of the mucosal membranes of the mouth caused by the chemoradiotherapy used to treat patients with oropharyngeal cancer. SOM prevents these patients from being able to drink and/or eat, and can increase hospitalization rates, cause interruption or termination of chemoradiotherapy before completion of treatment, and cause aspiration induced lung injury. SOM results in significant short- and long-term negative impacts on clinical outcomes and quality of life. There is no FDA-approved preventative or treatment option for the estimated >40,000 newly diagnosed individuals with oropharyngeal cancer in the US who may receive chemoradiation each year and are at-risk of developing SOM. Recent trials show that the majority of oropharyngeal cancer patients receiving chemoradiotherapy will develop SOM.

Validive is a once daily self-administered mucoadhesive tablet designed to prevent SOM in oropharyngeal cancer patients who receive chemoradiotherapy. Monopar is evaluating Validive in this patient population in the international Phase 2b/3 VOICE study. Updated highlights of this trial include:

43 clinical sites opened to date, active and enrolling patients in both the US and Europe
Interim analysis is currently anticipated to be reached in mid-2022. Further, based on timely findings extracted from public reporting of recently completed SOM trials, the Company is presently evaluating potential enhancements to and exact timing of the interim analysis
Camsirubicin – Phase 1b Dose-Escalation Trial, Actively Recruiting

Advanced soft tissue sarcoma (ASTS) is a diverse type of cancer that typically develops in the connective tissue of the body and which has metastasized (spread) or is not amenable to surgery. The average life expectancy from time of diagnosis for patients with ASTS is about 12 to 15 months. Doxorubicin is the current 1st line standard of care treatment for most types of ASTS.

Doxorubicin is FDA approved in 14 different types of cancers including soft tissue and bone sarcomas; metastatic stomach, ovarian, thyroid, lung, and breast cancer; acute myeloid and lymphoblastic leukemia; Hodgkin and non-Hodgkin lymphoma; and neuroblastoma, and is one of the most widely used cancer drugs around the world. It is a drug that becomes more effective at higher doses. Unfortunately, due to the potential development of irreversible heart damage, patients stop doxorubicin treatment once a certain cumulative lifetime dose limit threshold is reached. Dosing higher than this lifetime limit sharply increases the rate of irreversible heart damage. As a result, even if patients are responding to treatment, they discontinue doxorubicin treatment typically after only 6 to 8 cycles of doxorubicin.

Monopar is developing a novel proprietary analog of doxorubicin called camsirubicin. Camsirubicin has been designed to retain the anti-cancer activity while avoiding the irreversible heart damage that is seen with doxorubicin. The hypothesis behind the use of camsirubicin is straightforward: modifying doxorubicin in order to reduce cardiac damage could enable higher and longer dosing, resulting in better patient outcomes. The preclinical, Phase 1, and Phase 2 camsirubicin data generated to date support the potential to treat patients with high doses per cycle and for longer periods of time. No irreversible heart damage has been seen to date in any of the camsirubicin clinical trials.

The Company is currently enrolling patients in an open-label Phase 1b dose escalation trial in ASTS patients to evaluate higher doses of camsirubicin than have been used in the previous Phase 1 and Phase 2 trials. Although this Phase 1b is designed to determine the maximum tolerated dose of camsirubicin, given the historical dose-dependent anti-tumor response repeatedly demonstrated with doxorubicin, efficacy measurements are being tracked in these patients as the dose is increased. Updated highlights of this trial include:

Phase 1b dose-escalation trial initiated in September 2021, with first patients dosed in October 2021
First dose level completed in November 2021, with positive recommendation from trial safety review committee to proceed to next higher dose level
Three patients already dosed at the second dose level, which is a higher dose level than tested in any prior camsirubicin clinical trial
"Early signs of clinical benefit are being observed with camsirubicin in this Phase 1b trial, which is quite encouraging. Two of three patients in the first dose level have stable disease, one of which has liver metastases and experienced fairly quickly a reduction in pain and improved liver function tests," said Dr. Sant Chawla, Principal Investigator, Sarcoma Oncology Research Center in Santa Monica, CA. "The second cohort so far is also looking encouraging. We look forward to continuing to escalate the camsirubicin dose level to identify a new, higher recommended Phase 2 dose, and continuing to assess camsirubicin for evidence of antitumor activity."

Radiopharmaceutical Platform and MNPR-101

Monopar and NorthStar Medical Radioisotopes have extended their 50/50 radiopharmaceutical partnership for 2022. This collaboration has generated a radioimmunotherapeutic candidate, MNPR-101-PCTA, that is being evaluated as a potential diagnostic and therapeutic agent in cancer and severe COVID-19. Updated highlights of this program include:

Provisional composition of matter patents filed covering the Actinium-based radiopharmaceutical drug candidate (MNPR-101-PCTA-Ac-225)
Peer-reviewed publications highlighting the utility of MNPR-101 and MNPR-101 fragment conjugates as uPAR-targeted imaging agents in numerous cancers
Currently evaluating pathways to initiating a first-in-human study
MNPR-202

MNPR-202 is a novel analog of camsirubicin currently being evaluated in preclinical studies. It retains the same potentially non-cardiotoxic backbone as camsirubicin but has been modified at other positions, which may enable it to evade doxorubicin drug resistance mechanisms. Updated highlights of this program include:

Entered collaboration and commenced work with Cancer Science Institute of Singapore to evaluate activity of MNPR-202 in preclinical models of multiple cancers
Composition of matter patent covering MNPR-202 has been allowed in the US

On February 15, 2022 Incyte (Nasdaq:INCY) reported that it will present at the virtual Cowen 42nd Annual Health Care Conference on Monday, March 7, 2022 at 9:50 a.m. ET (Press release, Incyte, FEB 15, 2022, View Source [SID1234608113]).

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The presentation will be webcast live and can be accessed at Investor.Incyte.com and will be available for replay for 30 days.

On February 15, 2022 Ipsen (Euronext: IPN; ADR: IPSEY) reported two-year (25.4 months minimum; 32.9 months median) follow-up results from analyses of the Phase III CheckMate -9ER trial, which demonstrated sustained survival and response rate benefits (abstract #350)1, as well as health-related quality of life (HRQoL) improvements (abstract 323)2, with the combination of Cabometyx (cabozantinib) and Opdivo (nivolumab) versus sunitinib in the first-line treatment of advanced renal cell carcinoma (aRCC) (Press release, Ipsen, FEB 15, 2022, View Source [SID1234608108]). These updated results will be featured in two poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) from February 17 to 19, 2022.

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Dr. Cristina Suárez, M.D. PhD, Medical Oncologist at the Vall d´Hebron University Hospital, Barcelona, Spain and a lead investigator on the Phase III CheckMate -9ER trial said, "I am delighted to see the extent of the efficacy benefits demonstrated with the combination of Cabometyx and Opdivo in the CheckMate 9ER trial. These new data showcase the possibilities we can offer patients for their advanced disease, presenting the opportunity to significantly reduce their risk of death, and for some patients, achieve a complete response, whilst maintaining quality of life. There has been a dramatic evolution in the treatment landscape across lines of therapy for people living with renal cell carcinoma over recent years; this is an exciting time to be a treating physician in this area."

With a median follow-up of 32.9 months (25.4 months minimum), Cabometyx in combination with Opdivo continued to show superiority across efficacy endpoints of overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), including increased complete response (CR) rates compared to sunitinib.1 For the secondary endpoint of median OS, the combination demonstrated a maintained clinically meaningful improvement (37.7 months vs. 34.3 months), with a 30% reduction in the risk of death (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.55 to 0.90) compared to sunitinib.1 PFS benefits, the primary endpoint of the study, were also maintained, with the combination continuing to double median PFS vs. sunitinib (16.6 months vs. 8.3 months, respectively; HR: 0.56; 95% CI: 0.46 to 0.68).1 Additionally, both superior ORR and DCR benefits were shown to be sustained with increased follow-up for the combination versus sunitinib; ORR 55.7% vs 28.4% and DCR 88.2% vs 69.3%. Moreover, among patients treated with the combination, 12.4% had a complete response vs 5.2% for sunitinib.1 In a further exploratory analysis of depth of response in target lesions by organ site, a higher percentage of patients experienced tumor shrinkage benefits with Cabometyx in combination with Opdivo vs. sunitinib across all organ sites assessed (kidney, liver, lung, lymph node and bone).1

The safety profile identified in the CheckMate -9ER trial was consistent with that previously observed for Cabometyx and Opdivo. 97.2% of patients treated with the combination experienced a treatment-related adverse event (TRAE) of any grade, compared to 93.1% of patients treated with sunitinib.1 Overall, 10.6% discontinued Opdivo only, 9.1% discontinued Cabometyx only, and 7.5% discontinued both Cabometyx and Opdivo (simultaneously or sequentially).1

In a separate analysis, with 32.9 months median follow-up, patients continued to report clinically meaningful HRQoL benefits with Cabometyx in combination with Opdivo compared to sunitinib.2 These exploratory outcomes were measured using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19) which assessed quality of life (QoL) associated specifically to kidney cancer as well as EQ-5D-3L instruments which assessed QoL more generally. HRQoL scores from these instruments were found to be improved or maintained over time amongst patients treated with the combination, while reductions in scores were observed with sunitinib. Additionally, those who received the combination were 48% less likely to be notably bothered by treatment side effects than patients in the sunitinib arm.2 These updated data follow the publication of 23.5 month median follow-up HRQoL data in The Lancet Oncology, published on 12 January 2022.3

Steven Hildemann, M.D. PhD, Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and GlobalPatient Safety, Ipsen said "These new data from the CheckMate -9ER trial build on the previously demonstrated sustained efficacy benefits of the combination of Cabometyx and Opdivo, across patient risk groups. We are delighted to see that these extended survival benefits are further supported by a continued maintenance of health-related quality of life. Evaluating the patient perspective has been an integral element of the CheckMate -9ER trial analyses, ensuring that data are representative of the patient population and their priorities. With this growing body of evidence for the combination of Cabometyx and Opdivo, we are confident of the potential for these data to be realized in real world settings worldwide."

Ipsen thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

About renal cell carcinoma (RCC)

There were over 400,000 new cases of kidney cancer diagnosed worldwide in 2020.4 Of these, RCC is the most common type of kidney cancer, accounting for approximately 90% of cases.5,6 It is almost twice as common in men, and male patients account for over two thirds of deaths.4 If detected in the early stages, the five-year survival rate is high, but for people living with advanced or late-stage metastatic RCC, the survival rate is much lower, around 12%, with no identified cure for this disease.7,8

About the CheckMate -9ER trial

CheckMate -9ER was an open-label, randomized, multi-national Phase III trial evaluating people living with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus Opdivo (n= 323) versus sunitinib (n= 328). The primary endpoint is progression-free survival (PFS). The secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis compared the doublet combination versus sunitinib in all randomized patients. The trial was sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Cabometyx (cabozantinib)

In the U.S., Cabometyx tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. Outside the U.S., Cabometyx is currently approved in 60 countries, including in the European Union, Great Britain, Norway, Iceland, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong Kong, Singapore, Macau, Jordan, Lebanon, the Russian Federation, Ukraine, Turkey, the United Arabic Emirates (U.A.E.), Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Malaysia, Colombia and Egypt for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, Great Britain, Norway, Iceland, Canada, Australia, New Zealand, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, the Russian Federation, Ukraine, Turkey, the U.A.E., Saudi Arabia, Israel, Serbia, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Egypt and Malaysia for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, Great Britain, Norway, Iceland, Canada, Australia, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, the Russian Federation, Ukraine, Turkey, Lebanon, the

U.A.E., Peru, Panama, Guatemala, Chile, the Dominican Republic, Ecuador, Thailand, Brazil, New Zealand, Egypt and Malaysia for HCC in adults who have previously been treated with sorafenib. Cabometyx is also approved in combination with nivolumab as first-line treatment for people living with advanced RCC, in the European Union, Great Britain, Norway, Iceland, Switzerland, Taiwan, Singapore, the U.A.E., Australia, Chile, Israel and the Russian Federation.

The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC) and in the U.S. Prescribing Information (USPI).

Ipsen has exclusive rights for the commercialization of Cabometyx outside the U.S. and Japan. Cabometyx is marketed by Exelixis, Inc. in the U.S. and by Takeda Pharmaceutical Company Limited in Japan. Cabometyx is a registered trademark of Exelixis, Inc.