On November 15, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage drug-development company focused on DNA-based immunotherapy and next-generation vaccines, reported financial results for the three and nine months ended September 30, 2021, and provided an update on clinical development programs with GEN-1, a DNA-based interleukin-12 (IL-12) immunotherapy in Phase II clinical development for the treatment of advanced-stage ovarian cancer (Stage III/IV), and ThermoDox, a proprietary heat-activated liposomal encapsulation of doxorubicin under investigator-sponsored development for several cancer indications (Press release, Celsion, NOV 15, 2021, View Source [SID1234595584]). In addition, Celsion has two feasibility-stage platform technologies for the development of novel nucleic acid-based immunotherapies and next-generation vaccines for infectious diseases.

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!

"GEN-1 continues to show momentum as patient enrollment nears 70% with full enrollment targeted by the first half of 2022. We are encouraged with surgical resection results at the 100 mg/m² dose cohort in the Phase II OVATION 2 Study. From the first 36 patients with interval debulking surgery, 80% treated with GEN-1 at a dose of 100 mg/m² plus neoadjuvant chemotherapy (NACT) had a complete tumor resection (R0), which indicates a microscopically margin-negative resection with no gross or microscopic tumor remaining in the tumor bed; this compares with 56% of patients in the control arm having R0 resections. These results are reasonably consistent with those reported from our earlier Phase I trials in advanced-stage ovarian cancer," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer.

"At the International Vaccines Congress in October, Celsion announced results from preclinical in vivo studies showing production of antibodies and cytotoxic T-cell response specific to the spike antigen of SARS-CoV-2 when immunizing BALB/c mice with our next-generation PLACCINE DNA vaccine," added Mr. Tardugno. "Our goal over the next several quarters is to demonstrate the superiority of Celsion’s multicistronic DNA vaccine over current mRNA vaccines with respect to the quality of immune response (higher affinity of neutralizing antibodies, IgG titers and T-cell response) against multiple SARS-CoV-2 variants, longer duration of immune response and a stable product at lower temperatures."

Recent Developments

GEN-1 Immunotherapy

Interim Data Reported on the OVATION 2 Study. Interim clinical data from the first 36 patients who have undergone interval debulking surgery are as follows:

●20 patients were treated with GEN-1 at a dose of 100 mg/m² plus NACT, with 16 out of 20 patients (80%) having R0 resections.
●16 patients were treated with NACT only, with 9 out of 16 patients (56%) having R0 resections.
●When combining these results with the surgical resection rates observed in the Company’s prior Phase Ib dose-escalation trial (the OVATION 1 Study), a population of patients with inclusion criteria identical to the OVATION 2 Study, the data reflect the strong dose-dependent efficacy of adding GEN-1 to NACT.

●The objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for the 16 patients treated with NACT only were comparable, as expected, to the 20 patients treated with GEN-1 at a dose of 100 mg/m² plus NACT, with both groups demonstrating an approximate 80% ORR.
Publication of OVATION 1 Study in the Journal of Clinical Cancer Research. In July 2021, the Company announced the publication of data from its Phase 1b OVATION 1 Study with GEN-1 in combination with NACT in patients with advanced ovarian cancer in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The study, authored by Premel H. Thaker, M.D. et al. and titled "GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-Escalation Study," is available here. Dr. Thaker, Professor of Gynecologic Oncology and Director of Gynecologic Oncology Clinical Research at the Washington University School of Medicine in St. Louis, is the study chair for the OVATION program.

The OVATION 1 Study enrolled 18 patients with newly diagnosed stage IIIC and IV epithelial ovarian cancer in a standard 3+3 dose-escalation design testing four GEN-1 doses (36 mg/m2, 47 mg/m2, 61 mg/m2 and 79 mg/m2) in combination with NACT (carboplatin-paclitaxel). There were 15 patients evaluable for safety, and 14 underwent interval debulking and were evaluable for RECIST.

As previously reported, there were no dose-limiting toxicities. As shown in the chart below, in the two highest doses of GEN-1 the objective response rate was 100% and the R0 resection rate was 88%. Newly published data show the CRS, which was analyzed in this paper for the first time, was 50% in the two highest doses of GEN-1, compared with 28% from a major publication evaluating CRS scoring.

Clinical Responses: Tumor Response, Surgical Outcome, Pathological Response and Chemotherapy Response Score with NAC/GEN-1 Escalating Doses

Translational Responses: IL-12 and IFN-γ Levels, Response to Immune-Suppressive Agents; Ratio of CD8+ Cells to Immune Suppressive Agents

●A dose-dependent increase in immunostimulatory cytokines IL-12 and its downstream cytokine IFN-γ in ascitic fluid. The anticancer effects of these cytokines are widely recognized in human malignancies.
●The proportion of myeloid dendritic cells in the peritoneal fluid trended higher (3.1-fold) accompanied by a similar 3.0-fold rise in CD8+ cells.
●GEN-1 appeared to reduce four immunosuppressive signals (Foxp3, IDO1, PD-1 and PD-L1) within the tumor microenvironment, a trend not seen with NAC therapy alone.
●GEN-1 appeared to stimulate the body’s immune system through the production of CD4 and CD8 cells.
●GEN-1 gene therapy was associated with an apparent increase in the cytotoxic state of T cells within the tumor microenvironment as indicated by the increases in the ratios of CD8+/CD4+ and CD8+/Treg cells. Indeed, higher CD8+/CD4+ T cell and CD8+/Treg ratios are considered prognostic for prolonged survival.

Vaccine Initiative

Vaccine Advisory Board Expanded. In July 2021, the Company announced the addition of Dan H. Barouch, M.D., Ph.D. and Luke D. Handke, Ph.D. to its Vaccine Advisory Board (VAB). They joined Britt A. Glaunsinger, Ph.D. and Xinzhen Yang, M.D., Ph.D. on the VAB, which was formed in February 2021.

Dr. Barouch is the principal investigator at the Barouch Laboratory, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and William Bosworth Castle Professor of Medicine at Harvard Medical School. In addition, he is a key participant in the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery, the National Institutes of Health Martin Delaney HIV-1 Cure Collaboratory and the Ragon Institute of MGH, MIT and Harvard. Dr. Barouch and his team were instrumental in developing the vector, a variant of an adenovirus called Ad26, that was used to make single-dose vaccines for HIV, tuberculosis and Zika, and ultimately, in conjunction with Johnson & Johnson researchers, SARS-CoV-2. He has authored numerous peer-reviewed articles.

Dr. Handke is a highly skilled molecular biologist and microbiologist with a decade of pharmaceutical industry experience including nine years with Pfizer’s Vaccine Research and Early Development Unit. At Pfizer he served as molecular biology lead on an early phase viral vaccine program and was the lead reviewer of data sources and literature citations for licensure application for the Trumenba meningococcal group B vaccine in the U.S. and in Europe. He began his career in vaccine research at Wyeth. He is co-author and co-inventor on various patent applications for a protein-based RSV vaccine and a SARS-CoV-2 detection assay and authored 10 peer-reviewed publications including six as first author. Dr. Handke is currently a Senior Scientist at the University of Nebraska Medical Center in Omaha. In addition to serving on the VAB, Dr. Handke will provide consulting services to Celsion in connection with its vaccine-development program, which involves DNA-based vectors in combination with proprietary non-viral cellular delivery agents. He also will advise Celsion as it advances this program into human clinical studies.

Results from In Vivo Studies with PLACCINE DNA Vaccine Platform Indicate Immune Response Against SARS-Cov-2. In September 2021, the Company announced results from preclinical in vivo studies showing production of antibodies and cytotoxic T-cell response specific to the spike antigen of SARS-CoV-2 when immunizing BALB/c mice with the Company’s next-generation PLACCINE DNA vaccine platform. Moreover, the antibodies to SARS-CoV-2 spike antigen prevented the infection of cultured cells in a viral neutralization assay. The production of antibodies predicts the ability of PLACCINE to protect against SARS-CoV-2 exposure, and the elicitation of cytotoxic T-cell response shows the vaccine’s potential to eradicate cells infected with SARS-CoV-2. These findings demonstrate the potential immunogenicity of Celsion’s PLACCINE DNA vaccine, which is hypothesized to provide broad-spectrum protection and resistance against variants by incorporating multiple viral antigens, to improve vaccine stability at storage temperatures of 4oC and above, and to facilitate cheaper and easier manufacturing. Celsion reported these data at the International Vaccines Conference in October 2021.

Agreement with Hainan Poly Pharm to Manufacture Celsion’s DNA-based Vaccine. In September 2021, the Company announced an amendment to its existing contract manufacturing agreement with Hainan Poly Pharm Co. Ltd., a generics manufacturer dedicated to providing therapeutic-value products and services to patients and customers around the world, to include development work for the Company’s investigational DNA-based COVID-19 vaccine. Under the terms of the amended agreement, Poly Pharm will manufacture clinical batches and, if approved for use, will also manufacture commercial batches for Celsion’s vaccine based on its TheraPlas technology. Poly Pharm is experienced with chemistry, manufacturing and controls (CMC), process development and good manufacturing processes (cGMP), including process optimization and manufacturing services to help customers advance new drug development projects. Its sites and pharmaceutical compounds have been approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), China’s National Medical Products Administration (NMPA) and the World Health Organization (WHO).

Oral Presentation on Celsion’s Ongoing Work with DNA-based Vaccines at International Vaccines Congress. In October 2021, the Company announced that Khursheed Anwer, Ph.D., executive vice president and chief science officer, presented at the International Vaccines Congress . Dr. Anwer’s presentation was titled "Immunogenicity of DNA Vaccines based on Multicistronic Vectors and Synthetic DNA Delivery Systems" and can be viewed here. Dr. Anwer discussed ongoing proof-of-concept studies in SARS-CoV-2 with the Company’s DNA-based vaccine approach utilizing its PLACCINE platform. PLACCINE, Celsion’s proprietary design for DNA vectors, encompasses molecular elements designed to improve the immune response by targeting multiple antigens of a pathogen or multiple mutants of the same antigen. Dr. Anwer also reviewed the PLACCINE technology and the production of a family of DNA vaccine vectors expressing one or more SARS-CoV-2 surface antigens as a proof-of-concept target, verified vector composition and demonstrated expression of the encoded genes.

Corporate Developments

Presentations at Three Healthcare Investment Conferences. Celsion management made presentations at the following investment conferences in October:

●Chardan’s 5th Annual Genetic Medicines Conference. Michael H. Tardugno, Celsion’s chairman, president and chief executive officer, and Khursheed Anwer, Ph.D., Celsion’s chief scientific officer, participated in a fireside chat.
●LD Micro Main Event. Jeffrey W. Church, Celsion’s chief financial officer, presented virtually.
●Alliance Global Partners’ Virtual Healthcare Conference. Mr. Tardugno participated in an oncology focused panel discussion moderated by James Molloy, Research Analyst.

Third Quarter Financial Results

For the quarter ended September 30, 2021, Celsion reported a net loss of $5.4 million ($0.06 per share), compared with a net loss of $8.1 million ($0.24 per share) in the same period of 2020. Operating expenses were $5.2 million in the third quarter of 2021, which represented a $0.9 million (21%) increase from $4.3 million in the same period of 2020.

The Company ended the third quarter of 2021 with $60.6 million in cash, investment securities, restricted cash and accrued interest receivable. Coupled with future sales of unused New Jersey NOL’s, the Company believes it has sufficient capital resources to fund its operations through the end of 2024.

Research and development (R&D) expenses were $2.5 million in the third quarter of 2021, consistent with $2.5 million reported in the third quarter of 2020. Costs associated with the OVATION 2 Study were $0.2 million in each of the third quarters of 2021 and 2020. R&D costs associated with both the development of GEN-1 to support the OVATION 2 Study and the development of the PLACCINE DNA technology platform increased to $1.1 million in the third quarter of 2021, compared with $0.7 million in the same period of 2020. Clinical development costs for the Phase III OPTIMA Study decreased $0.3 million to $0.2 million in the third quarter of 2021, compared with $0.5 million in the third quarter of 2020, due to the discontinuation of this 556-patient trial in the first quarter of 2021. Other costs related to clinical supplies and regulatory support for the Company’s clinical development programs decreased to $1.0 million in the third quarter of 2021 from $1.1 million in the third quarter of 2020, largely driven by higher manufacturing costs for GEN-1 clinical supplies for the Phase II portion of the OVATION 2 Study, offset by lower regulatory and manufacturing costs related to the OPTIMA Study.

General and administrative expenses were $2.7 million in the third quarter of 2021, compared with $1.8 million in the same period of 2020. The $0.9 million increase was primarily attributable to higher non-cash stock-compensation expense ($0.2 million), an increase in legal and professional fees ($0.6 million) and an increase in Directors’ and Officers’ insurance premiums ($0.1 million).

Non-operating expenses of $0.3 million in the third quarter of 2021 decreased from $3.9 million in the third quarter of 2020 due to (i) a non-cash charge of $1.1 million for the change in valuation of the earn-out milestone liability for the GEN-1 ovarian product candidate recognized in the third quarter of 2020 compared with a $0.3 million non-cash charge recognized in the current quarter; (ii) a non-cash charge of $2.4 million related to the impairment of certain in-process research and development assets related to the development of the Company’s glioblastoma multiforme (GBM) cancer product candidate in the third quarter of 2020; and (ii) lower interest expense of $0.4 million on the Company’s debt facilities in the current quarter, compared with the comparable prior year period. In June 2021, the Company entered into a new $10.0 million loan facility with SVB, with a portion of the proceeds used to retire all outstanding indebtedness under the Company’s venture debt facility entered in late June 2018 with Horizon Technology Finance Corporation.

Nine Month Financial Results

For the nine months ended September 30, 2021, the Company reported a net loss of $16.5 million ($0.21 per share), compared with a net loss of $18.5 million ($0.62 per share) in the same period of 2020. Operating expenses were $15.9 million during the first nine months of 2021, which represented a $1.8 million (13%) increase from $14.1 million in the same period of 2020.

Net cash used for operating activities was $11.1 million in the first nine months of 2021, compared with $11.9 million in the same period in 2020. This was in line with the Company’s projected cash utilization for 2021 of approximately $17 million, or an average of approximately $4.25 million per quarter. Cash provided by financing activities of $54.8 million during the first nine months of 2021 was derived from equity offerings in January 2021 and April 2021, the $10 million loan facility with SVB in June 2021 and the sale of the Company’s unused New Jersey NOLs in May 2021.

Research and development expenses decreased $0.9 million to $7.6 million in the first nine months of 2021 from $8.5 million in the comparable prior-year period. Costs associated with the OVATION 2 Study increased to $1.0 million in the first nine months of 2021 compared to $0.7 million in the same period of 2020. The Company initiated enrollment in the Phase 2 portion of the study during the third quarter of 2020. R&D costs associated with the development of GEN-1 to support the OVATION 2 Study as well as development of the PLACCINE DNA technology platform increased to $3.1 million in the first nine months of 2021, compared with $2.3 million in the comparable 2020 period. Costs for the Phase III OPTIMA Study decreased $1.2 million to $0.6 million in the first nine months of 2021, compared with $1.8 million in the first nine months of 2020, due to the discontinuation of this trial in the first quarter of 2021. Other costs related to clinical supplies and regulatory support for the Company’s clinical development programs decreased $0.8 million to $2.9 million in the first nine months of 2021, compared with the same prior-year period due to lower regulatory and manufacturing costs for the discontinued Phase III OPTIMA Study.

General and administrative expenses were $8.3 million in the first nine months of 2021, compared with $5.5 million in the same period of 2020. The $2.8 million increase was primarily attributable to higher non-cash stock-compensation expense ($1.0 million), an increase in legal and professional fees ($1.4 million) and an increase in Directors’ and Officers’ insurance premiums ($0.2 million).

Other expenses during the first nine months of 2021 included a non-cash charge of $0.3 million for the change in valuation of the earn-out milestone liability for the GEN-1 ovarian product candidate, compared with a non-cash charge of $1.4 million during the comparable prior-year period and a non-cash charge of $2.4 million related to the impairment of certain in-process research and development assets related to the development of the Company’s GBM cancer product candidate in the third quarter of 2020. In connection with the Company’s venture debt facilities, the Company incurred interest expense of $0.5 million during the first nine months of 2021, compared with $1.1 million during the same period in 2020. In June 2021, the Company entered into a new $10.0 million loan facility with SVB, with a portion of the proceeds used to retire all outstanding indebtedness under the Company’s venture debt facility with Horizon Technology Finance Corporation.

Conference Call

The Company will host a conference call to provide a business update, discuss its third quarter 2021 financial results and answer questions at 11:00 a.m. ET today. To participate in the call, please dial 1-800-353-6461(Toll-Free/North America) or +1-334-323-0501 (International/Toll) and ask for the Celsion Corporation Third Quarter 2021 Earnings Call (Conference Code: 4154518). The call will also be broadcast live on the internet at www.celsion.com. The call will be archived for replay through December 1, 2021. The replay can be accessed at +1-719-457-0820 or 888-203-1112 using Conference ID: 4154518. An audio replay will also be available on the Company’s website, www.celsion.com, for 90 days after 2:00 p.m. ET on November 15, 2021.

On November 15, 2021 Portage Biotech Inc., (NASDAQ: PRTG) ("Portage" or the "Company"), a clinical-stage immuno-oncology company developing therapies to improve patient lives and increase survival by avoiding and overcoming cancer treatment resistance, reported that data being presented by Intensity Therapeutics during the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting and the Connective Tissue Oncology Society (CTOS) Annual Meeting (Press release, Portage Biotech, NOV 15, 2021, View Source [SID1234595583]). Data from the Phase 2 IT-01 trial shows that Intensity’s lead asset, INT230-6 (PORT-1) is well tolerated with direct tumor-killing effects, both as a monotherapy and in combination with the approved checkpoint inhibitors pembrolizumab and ipilimumab. Highlights from the presentations are included below.

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 promising results showcased in these presentations validate the broad treatment potential of INT230-6 (PORT-1) in multiple treatment regimens – alone, in combination with a PD-1 antibody and in combination with a CTLA-4 antibody – and show substantially longer survival when compared to historical data," said Dr. Ian Walters, Chief Executive Officer of Portage Biotech and Chief Medical Officer of Intensity. "The company has amassed data in over 110 patients and the continual favorable safety and efficacy profile bodes well for this therapy’s potential as a treatment for metastatic cancers that have been historically challenging to treat, including soft tissue sarcoma. We look forward to working with our collaborators at Intensity to initiate a randomized Phase 3 study in 2022 and to further exploring how INT230-6 (PORT-1) can impact survival and improve quality of life for these patients."

INT230-6 (PORT-1) is a novel intratumoral amphiphilic formulation developed by Intensity Therapeutics, a company affiliated with Portage. It delivers potent cancer-killing agents directly into the tumor to immediately reduce cancer burden, break down the cytokine wall and recruit immune cells to attack residual disease. The Phase 2 IT-01 trial is governed by joint development committees with Bristol Myers Squibb and Merck, in which Dr. Walters contributes as a representative of Intensity Therapeutics.

SITC 2021

Presentation Details:

Poster #501: Survival and Immune Response Data from Intratumoral INT230-6 Alone (IT-01) and with Pembrolizumab [KEYNOTE-A10] in Subjects with Locally Advanced, Unresectable and Metastatic Solid Tumors
Poster #536: Intratumoral INT230-6 shows a favorable safety profile and early signs of efficacy in advanced soft tissue sarcoma with monotherapy and in combination with Ipilimumab [Intensity IT-01; BMS#CA184-592]
Data Highlights:

INT230-6 demonstrates direct tumor killing in injected lesions
Immunohistochemistry analysis and abscopal results in non-injected lesions indicate dosing INT230-6 may also activate a T-cell mediated immune response
INT230-6 injection into tumors appears to be a promising approach in treating metastatic disease alone and in combination with immunotherapies
Biopsies from tumors treated using INT230-6 showed substantial tumor necrosis, reduction of viable cancer, a decreased cancer proliferation as measured by Ki67, and increased tumor infiltrating lymphocytes such as CD4 and CD8 T-cells
Exploratory analysis suggests promising survival for subjects receiving INT230-6 compared to historical standards
CTOS 2021

Presentation Details:

Paper #33: Safety and efficacy from a phase 1/2 study of intratumoral INT230-6 alone or in combination with ipilimumab [Intensity# it-01; BMS# ca184-592] in adult subjects with metastatic sarcomas (NCT 03058289)
Data Highlights:

Preliminary data suggests that INT230-6 (PORT-1), as a monotherapy, demonstrates direct tumor killing in soft tissue sarcoma subjects that can elicit an anti-cancer immune response
INT230-6 (PORT-1) was also shown to be well tolerated either as a monotherapy or in combination with checkpoint inhibitor ipilimumab
Exploratory analysis suggests promising survival with dosing, based on total tumor burden, as compared to historic survival from historical sarcoma studies
To view the full announcement from Intensity Therapeutics, visit their website at www.intensitytherapeutics.com.

About PORT-1
INT230-6 (PORT-1) contains amphiphilic molecules combined with anti-cancer payloads, offering a next-generation formulation to safely deliver up to three times the systemic dose of cancer-killing agents directly into tumors. PORT-1 breaks down the cytokine wall and stimulates immune cells to process tumor antigens and attack residual disease. Used alone or in combination with checkpoint inhibitors, PORT-1 may lead to improved survival with dramatically fewer unwanted side effects. PORT-1 has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for triple-negative breast cancer, demonstrating the importance of ongoing drug development and improved therapies for this aggressive type of cancer. Select members of the Portage management team contribute to the development efforts led by Intensity Therapeutics.

About Intensity Therapeutics
Intensity Therapeutics, Inc. is a privately held, clinical-stage biotechnology company pioneering a new immune-based approach to treat solid tumor cancers. Intensity leverages its DfuseRx℠ technology platform to create new, proprietary drug formulations that following direct injection rapidly disperse throughout a tumor and diffuse therapeutic agents into cancer cells. Intensity’s product candidates have the potential to induce an adaptive immune response that not only attacks the injected tumor but also non-injected tumors. The Company executed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute’s (NCI) Vaccine Branch in 2014 and has partnerships with Merck and Bristol Myers Squibb. For more information, please visit www.intensitytherapeutics.com and follow us on Twitter @IntensityInc.

On November 15, 2021 UroGen Pharma Ltd. (Nasdaq: URGN), a biopharmaceutical company dedicated to building and commercializing novel solutions that treat urothelial and specialty cancers, reported financial results for the third quarter ended September 30, 2021, and provided an overview of the Company’s recent developments (Press release, UroGen Pharma, NOV 15, 2021, View Source [SID1234595582]).

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 third quarter of 2021 was one of continued progress at UroGen, both clinically and commercially," said Liz Barrett, President and Chief Executive Officer of UroGen. "As we highlighted at our Spotlight Event last week, we will initiate a new single-arm Phase 3 study of UGN-102 in low-grade, intermediate-risk, non-muscle invasive bladder cancer. We believe this new design affords a higher probability of regulatory success for UGN-102 in patients with low-grade IR-NMIBC, while allowing us to remain on-track for a planned NDA submission in 2024." She added, "Additionally, as we approach the close of 2021, we are pleased with the strong demand we’re seeing for Jelmyto. September and October marked our highest months ever for both new patient starts and patient enrollment forms. We look forward to a strong start to 2022, as we advance and grow our pipeline while furthering the adoption of Jelmyto with the goal of it becoming the standard of care for patients with low-grade UTUC."

Business Highlights:

Jelmyto (mitomycin) for pyelocalyceal solution:

Achieved highest-ever Patient Enrollment Forms and New Patient Starts in September and October 2021.
UroGen generated net product revenue of $11.4 million for the third quarter of 2021, representing over 200% growth over the third quarter of 2020 (first full quarter of launch), this compares to $13.0 million in the second quarter of 2021.
As of November 1, 2021, 706 sites have been activated, which means they have completed their internal processes and have treated or are ready to treat patients. This represents a 73% increase since August 1, 2021.
Sites that have treated more than one patient as of November 1, 2021, increased to 86, compared to 63 as of August 1, 2021: an increase of approximately 37%.
UGN-102 (mitomycin) for intravesical solution:

Following discussions with the U.S. Food & Drug Administration (FDA), the Company announced plans to conduct a new single-arm Phase 3 study of UGN-102 for the treatment of low-grade, intermediate risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The trial, which is expected to initiate in early 2022, will be similar in design to the Company’s previous OPTIMA II study. Based on the results of the OPTIMA II study, the Company believes this new trial carries a high probability of demonstrating a significant benefit for patients.
Based on the planned initiation of this new Phase 3 study of UGN-102, the Company has ceased enrollment in the ATLAS Phase 3 trial of UGN-102 in LG-IR-NMIBC. The Company plans to complete ongoing treatments and follow up for all patients currently enrolled in the therapy arm. Safety data from the ATLAS study is expected to be included in a planned regulatory submission for UGN-102.
UGN-301:

Preclinical studies conducted to-date suggest that bladder cancer treated with a combination of TLR-7 agonist and an anti-CTLA4 antibody in RTGel, produces improved survival compared to treatment with other checkpoint inhibitors in RTGel, either alone or in combination with UGN-201.
Non-human primate toxicity studies underway to facilitate the initiation of a multi-arm Phase 1 study of UGN-301 in combination with other agents.
First-in-human study planned to start in the first half of 2022.
Geographic expansion:

Initiated a named-patient access program for Jelmyto in France, Germany, Switzerland, Austria and the UK.
Third Quarter 2021 Financial Results:

Jelmyto Revenue: UroGen reported net product revenue of Jelmyto for the third quarter ended September 30, 2021 of $11.4 million. Net product revenue was $31.9 million for the first three quarters of 2021 compared to $3.8 million for the same period in 2020 due to the launch of Jelmyto in June 2020.

R&D Expense: Research and development expenses for the third quarter ended September 30, 2021 were $11.9 million, including non-cash share-based compensation expense of $1.0 million. This compares to $10.2 million, including non-cash share-based compensation expense of $1.5 million, for the same period in 2020. The increase of $1.7 million is primarily attributable to the launch of our Phase 3 ATLAS study for UGN-102 at the end of 2020, and development cost of UGN-301, partially offset by a decrease in R&D expense related to Jelmyto.

SG&A Expense: Selling, general and administrative expenses for the third quarter ended September 30, 2021 were $21.6 million, including non-cash share-based compensation expense of $4.5 million. This compares to $22.1 million, including non-cash share-based compensation expense of $5.2 million, for the same period in 2020. The $0.5 million decrease is primarily attributable to higher launch related commercial spend in 2020.

Financing on Prepaid Forward Obligation: UroGen reported financing expense related to the prepaid forward obligation to RTW Investments of $6.8 million for the third quarter ended September 30, 2021.

Net Loss: UroGen reported a net loss of $30.2 million, or basic and diluted net loss per ordinary share of $1.35, for the third quarter ended September 30, 2021. This compares to $28.8 million, or basic and diluted net loss per ordinary share of $1.31, for the same period in 2020.

Cash & Cash Equivalents: As of September 30, 2021, cash, cash equivalents and marketable securities totaled $110.3 million.

2021 Operating Expense and Revenue Guidance: The Company is reducing its anticipated full year 2021 operating expenses to the range of $137 million to $142 million, from $155 million to $165 million, the new guidance includes non-cash share-based compensation expense of $22 to $25 million, subject to market conditions. In addition, the Company is providing full year 2021 revenue guidance of $47 million to $51 million.

Conference Call & Webcast Information:

Members of UroGen’s management team will host a live conference call and webcast today at 10:00 AM Eastern Time to review the Company’s financial results and provide a general business update.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call (855) 765-5685 (U.S.) or (615) 247-5916 (International) to listen to the live conference call. The conference ID number for the live call will be 1908609. An archive of the webcast will be available for two weeks on the Company’s website.

About Jelmyto

Jelmyto (mitomycin) for pyelocalyceal solution, is a drug formulation of mitomycin indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). Utilizing the RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, Jelmyto is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. Jelmyto is delivered to patients using standard ureteral catheters or nephrostomy tube. The U.S. FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to Jelmyto for the treatment of LG-UTUC. On April 15, 2020, the FDA approved Jelmyto, making it the first drug approved for the treatment of LG-UTUC in adult patients.

APPROVED USE FOR JELMYTO

JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC).

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO.
Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose.

Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.

are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda/gov/medwatch or call 1‑800‑FDA‑1088. You may also report side effects to UroGen Pharma at 1-855-987-6436.

Please see JELMYTO Full Prescribing Information, including the Patient Information, for additional information.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as upper tract urothelial cancers (UTUC). In the U.S., there are approximately 6,000 – 7,000 new or recurrent low-grade UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an investigational drug formulation of mitomycin in Phase 3 development for the treatment of low-grade intermediate risk non-muscle invasive bladder cancer. Utilizing the RTGelTM Technology Platform, UroGen’s proprietary sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter. The Company presented results from the Phase 2b OPTIMA II trial in September 2021.

About the Phase 3 ATLAS Trial

ATLAS was a global, open-label, randomized controlled Phase 3 trial designed to assess the efficacy and safety of UGN-102, with or without transurethral resection of bladder tumor (TURBT), versus TURBT alone in patients diagnosed with low-grade intermediate risk non-muscle invasive bladder cancer (LG-IR-NMIBC), defined as 1 or 2 of the following: new or recurrent multifocal bladder tumors, a solitary new or recurrent tumor >3 cm, or LG-IR-NMIBC recurrence in less than 12 months following a prior tumor diagnosis requiring endoscopic surgical resection or ablation.

Patients were randomized 1:1 to either UGN-102 or TURBT. Patients in the UGN-102 arm were treated with six weekly intravesical instillations of UGN-102. At the 3-month time point, patients were assessed for response. Patients who have demonstrated a complete response to either UGN-102 or TURBT, will continue for long-term follow-up for evidence of recurrence. Patients who demonstrate presence of persistent disease at 3-months, in either arm, will undergo a TURBT and then will also continue for long-term follow up for evidence of recurrence. The primary endpoint of the study was disease free survival. On November 10, 2021, the Company announced that, following discussions with the U.S. Food & Drug Administration, it has ceased enrollment in the ATLAS study and plans to initiate a new, single-arm Phase 3 study of UGN-102 in early 2022. All patients enrolled in the treatment arm of ATLAS will continue to receive treatment and undergo follow up.

Learn more about the ATLAS trial at www.clinicaltrials.gov (NCT04688931)

On November 15, 2021 Ascendis Pharma A/S (Nasdaq: ASND) provided an update on the Company’s previously reported $25 million American Depositary Shares (ADS) Share Repurchase Program. Each ADS represents one ordinary share of Ascendis Pharma A/S (Press release, Ascendis Pharma, NOV 15, 2021, View Source [SID1234595581]). The program was executed under Rules 10b-18 and 10b5-1 of the U.S. securities regulations.

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!

Under the program initiated on November 1, 2021, Ascendis Pharma A/S has repurchased shares for an amount up to $25 million in the period from November 1, 2021 to November 9, 2021 and the program is completed.

Since the announcement as of November 8th, 2021, the following transactions have been executed.

Trade Date

Number of ADS
Weighted Average
Purchase Price

Total Value*
Accumulated, last announcement 122,422 $19,763,252
November 8, 2021 26,800 $161.84 $4,338,140
November 9, 2021 5,615 $159.99 $898,492
Purchased under the program 154,837 $161.43 $24,999,884
*Total value includes fees and costs associated with the repurchase program.

Following these transactions, Ascendis Pharma A/S repurchased a total of 154,837 ADSs under the Share Repurchase Program.

On November 15, 2021 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported updated interim clinical data from the Phase 2 expansion cohort of its ongoing Phase 1/2 clinical trial evaluating ONCT-216 (formerly TK216), an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins, in patients with relapsed or refractory Ewing sarcoma (Press release, Oncternal Therapeutics, NOV 15, 2021, View Source [SID1234595580]). The data update was delivered in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2021 Virtual Annual Meeting.

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!

Session Title: Session 12: Ultra-Rare and Translocation Sarcomas
Session Date: Saturday, November 13, 2021
Presentation Title: Paper 74 – TK216 FOR EWING SARCOMA- INTERIM PHASE 1/2 RESULTS
A copy of the presentation will be accessible on the Events & Presentations page of the Investors section on the Company’s website at investor.oncternal.com.

"We remain encouraged by the two complete responses to ONCT-216 in heavily pre-treated patients with relapsed or refractory Ewing sarcoma, including one patient who had a durable CR for 24 months on treatment, and remains with no evidence of disease off of all treatments for several months," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We believe that an intensified dosing schedule, which we are investigating in a new study cohort that is now enrolling, holds promise to address the significant unmet needs for patients suffering from this devastating disease."

ONCT-216 remains generally well tolerated. As of the October 1, 2021 data cutoff date, the most common drug-related adverse events included myelosuppression, fatigue, alopecia, nausea, pyrexia, and decreased appetite. The myelosuppression was primarily neutropenia, which was transient and readily managed. No unexpected off-target toxicities have been observed.

About Ewing sarcoma

Ewing sarcoma is the second most common bone tumor among children and adolescents. The median age at diagnosis of patients with Ewing sarcoma is 15, the incidence is about 3 cases per 1 million per year in children under the age of 20 and about 1.3 cases per 1 million overall in the U.S. and prevalence is about 12 per million people overall in the US. Nearly all Ewing sarcoma cases are driven by translocations of ETS family oncogenes, including 85-90% of cases driven by the EWS-FLI1 fusion, and approximately 10% by EWS-ERG. Patients diagnosed with metastatic disease have five-year survival rates between 18% and 30%. The prognosis for patients with recurrent Ewing sarcoma is particularly poor, and five-year survival after recurrence is approximately 10 to 15%.

About ONCT-216

ONCT-216 is an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as diffuse large B-cell lymphoma (DLBCL), prostate cancer and acute myeloid leukemia (AML). ONCT-216 was developed based on discoveries in the laboratory of Jeffrey Toretsky, M.D., at Georgetown Lombardi Comprehensive Cancer Center, who discovered inhibitors of EWS-FLI1 using a novel chemical screening assay. In preclinical models, ONCT-216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to ONCT-216 for the treatment of Ewing sarcoma. ONCT-216 is an investigational medication that has not been approved by the FDA for any indication.

About the Study

ONCT-216 is being evaluated in a Phase 1/2 clinical study as a single agent and in combination with vincristine in heavily pretreated patients with relapsed or refractory Ewing sarcoma, a rare pediatric cancer with no standard treatment available after first-line chemotherapy. The current Phase 2 expansion cohort targeting up to 21 evaluable Ewing sarcoma patients is active and enrolling patients, designed to evaluate clinical responses to single agent ONCT-216 using an optimized dosing regimen, treating for 28 days per cycle, to intensify the amount of ONCT-216 administered over time. This multi-center study is currently enrolling patients at nine clinical trial centers across the U.S. Additional information about the ONCT-216 study may be accessed at ClinicalTrials.gov (NCT02657005).