On March 14, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported its corporate highlights and audited financial results for the full year 2023 (Press release, Molecular Partners, MAR 14, 2024, View Source [SID1234641180]).

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"2023 was a year of successful innovation and execution on our strategy, focusing on novel mechanisms that we believe only DARPin therapies can deliver. The encouraging new clinical and preclinical data across our portfolio illustrate the versatility and differentiated promise of DARPin therapies and our long-term leadership in this field," said Patrick Amstutz, Ph.D. Molecular Partners’ Chief Executive Officer. "In 2024, we look forward to presenting further clinical data from our lead oncology program MP0533, and translating our significant progress across the Radio-DARPin Therapy and Switch-DARPin platforms into initiation of IND-enabling studies."

Research & Development

MP0533
In December 2023, the Company presented positive initial data from the first four dosing cohorts of its ongoing Phase 1/2a trial of MP0533 at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. Results from the first 11 patients treated with MP0533 indicated an acceptable safety profile as of the data cut-off across all four dosing regimens (DRs), with no dose-limiting toxicities observed. Two responders were observed at the time of presentation, including a patient achieving a complete response (CR) in DR 4 and another patient with morphological leukemia-free state (MLFS) in DR 3. These responses are particularly notable for having occurred at dose levels below those predicted as therapeutically active.

MP0533 is a novel tetra-specific T cell-engaging DARPin, which simultaneously targets the antigens CD33, CD123, and CD70 on AML cells as well as the immune activator CD3 on T cells. AML cells display higher co-expression at least two of these target antigens as compared with healthy cells. MP0533 binds with increasing avidity as the number of its target antigens present increases, dramatically favoring binding to AML cells over healthy cells. This unique avidity-driven mode of action is designed to enable T cell-mediated killing of AML cells while preserving a therapeutic window that minimizes damage to healthy cells.

The Phase 1/2a study is on track with dosing in DR 6 currently ongoing. The Company expects to present data from further cohorts receiving MP0533 in H1 2024. Based on current safety and tolerability data from the ongoing study, and based on discussion with treating investigators and key opinion leaders, a protocol amendment is being filed to expand enrollment to additional higher dose cohorts of MP0533 beyond the initially planned highest cohort (DR 7). The goal of the additional higher doses will be to explore the full potential efficacy of MP0533. The Company expects to enroll patients in the added higher cohorts seamlessly in H2 2024.

Switch-DARPin Platform
In 2023, the Company introduced the Switch-DARPin platform and presented data evidencing its mechanism-of-action. The Switch-DARPin platform represents a further evolution of the Company’s capabilities to deliver multispecific candidates to address different disease needs. The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multispecific DARPin candidates leading to activation only in the presence of defined antigens. The objective is conditional activation of a targeted immune response.

In January 2024, the first program from the Switch-DARPin platform was introduced at the 42nd Annual J.P. Morgan Healthcare Conference, namely a cKIT x CD16a x CD47 multispecific Switch-DARPin candidate designed as next-generation targeted conditioning regimen for hematopoietic stem cell transplantation (HSCT) in AML and other diseases benefiting from HSCT such as genetic diseases. The cKIT x CD16a x CD47 Switch-DARPin program is designed to induce exhaustive killing of stem cells to increase long-term disease control post HSCT for AML patients, including those with a poor cytogenetic risk profile, and those currently not eligible for standard high-intensity conditioning. Our intent is to extend the access to potentially curative HSCT for more patients with AML and beyond.

The target-by-target rationale for this program’s design is:

cKIT is critical for stem cell maintenance and renewal and thus expressed on both hematopoietic and leukemic stem cells.
The CD16a DARPin engages NK cells and macrophages to selectively kill cKIT-positive cells.
The Switch-DARPin will block the CD47 "don’t eat me" signal only when the molecule binds on cKIT-positive cells, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells.
The Company expects to present initial pre-clinical data from the first Switch-DARPin program cKIT x CD16a x CD47 in H1 2024 and to run preclinical proof-of-concept studies in H2 2024, which should provide strong translational efficacy data.

Radio-DARPin Therapy (RDT) Platform
In September 2023, Molecular Partners presented preclinical data from its RDT platform at the 36th Annual Meeting of the European Association of Nuclear Medicine (EANM) demonstrating a substantially increased tumor uptake of RDT candidates through an adjustment of systemic half-life, achieved by binding to the human serum albumin protein. These results expand on preclinical data that were previously reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in 2023 and highlight that surface engineering of the DARPin backbone into a "Stealth" DARPin can lead to marked reduction of RDT candidate reabsorption by kidneys, addressing a key challenge for protein-based radionuclide delivery vectors. At the 42nd Annual J.P. Morgan Healthcare Conference in January 2024, Molecular Partners presented data showing the reduction of kidney absorption through novel engineered Stealth DARPins as well as enhanced tumor uptake via half-life engineering for several targets. Achieving improved tumor uptake and reduced kidney reabsorption has enabled the expansion of the RDT pipeline and strategy for the RDT portfolio.

Furthermore, in January 2024, Molecular Partners and Orano Med entered a strategic collaboration to co-develop 212Pb-based RDTs for patients with solid tumors. The deal combines the power of DARPins, as a highly differentiated modality for tumor-targeted delivery of radioisotopes, with Orano Med’s leading capabilities in Targeted Alpha Therapy and supply to further advance the RDT platform and expand Molecular Partners’ RDT portfolio.

The tumor-associated protein Delta-like ligand 3 (DLL3) was selected as the target of the Company’s lead RDT program to be advanced into IND-enabling studies in H1 2024. Expression of DLL3 is low in healthy tissue but significantly increased in certain tumor types, providing an opportunity for selective targeting through the high affinity and specificity offered by DARPins. The initiation of clinical studies and first-in-human data are expected in 2025 through co-development with Orano Med. Molecular Partners also expects to nominate additional targets and RDT candidates in 2024.

In addition to the above updates, Molecular Partners continued to progress its RDT portfolio of projects in partnership with Novartis.

MP0317
In November 2023, the Company presented additional positive dose-escalation data from its Phase 1 study of MP0317 in patients with advanced solid tumors at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). These data from 46 patients corroborated earlier reported findings of MP0317-induced CD40 activation and related remodeling of the tumor microenvironment (TME). At the time of the presentation, MP0317 monotherapy continued to display a favorable safety profile across all dosing cohorts up to the highest planned dose.

MP0317 enables tumor-localized immune activation through simultaneously targeting the immunostimulatory protein CD40 and fibroblast activation protein (FAP). FAP is expressed in high amounts around tumors. Through this proposed mechanism of action, MP0317 is designed to activate immune cells specifically within the tumor microenvironment, potentially delivering greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

The Company expects to report the full dataset from the Phase 1 study dose-escalation in H1 2024.

Corporate Governance & Leadership Highlights

Dr. Philippe Legenne, M.D., MBA, MHS, assumed responsibilities as acting Chief Medical Officer in August 2023.

Dr. Legenne joined Molecular Partners in early 2020. Over this time, he has led the clinical development strategy and execution across the Molecular Partners portfolio. Prior to joining Molecular Partners, Philippe held positions of increasing responsibility at JNJ, GSK, and Novartis, both in the United States and Europe. In his most recent role prior to Molecular Partners, Philippe led the EU medical organization for the oncology portfolio at Amgen. He received his medical degree from the Université de Lille (France), an MBA from ESSEC Business School (Paris) and a Master’s degree in health economics from Université Paris Dauphine-PSL.​

Update to Class Action Lawsuit

On February 29, 2024 a putative class action complaint against the Company, its directors, and certain of its executive officers was dismissed in the Company’s favor, and the case has been ordered closed. The original case was filed on July 12, 2022 in the U.S. District Court for the Southern District of New York.

2023 Financial Highlights

In the financial year 2023, Molecular Partners recognized total revenues and other income of CHF 7.0 million (2022: CHF 189.6 million) and incurred total expenses of CHF 68.1 million (2022: CHF 73.0 million). This led to an operating loss of CHF 61.1 million for 2023 (2022: Operating profit of CHF 116.6 million). The net financial loss recorded in 2023 was CHF 0.9 million, compared to a net financial gain of CHF 1.2 million in 2022. This resulted in a 2023 net loss of CHF 62.0 million (2022: Net profit of CHF 117.8 million).

The net cash used in operating activities in 2023 was CHF 59.0 million (2022: Net cash from operating activities CHF 118.6 million). Including short-term time deposits, the cash and cash equivalents position decreased by CHF 62.2 million as compared to year-end 2022, to CHF 186.9 million as of December 31, 2023 (December 31, 2022: CHF 249.1 million). Total shareholders’ equity stood at CHF 176.4 million as of December 31, 2023, a decrease of CHF 58.8 million (December 31, 2022: CHF 235.2 million).

The Company’s cash position and short-term time deposits were CHF 186.9 million as per December 31, 2023, and continue to provide the Company with financial flexibility and a forecasted cash runway well into 2026.

The Company’s balance sheet remained debt-free in 2023. As of December 31, 2023, the Company employed 167.5 FTE (full-time equivalents), down 4% year-on-year. About 83% of the employees are employed in R&D-related functions.

Key figures as of December 31, 2023

Key Financials (CHF million, except per share, FTE data) FY 2023 FY 2022 Change
Total revenues and other income 7.0 189.6 (182.6 )
R&D expenses (48.7 ) (50.7 ) 2.0
SG&A expenses (19.4 ) (22.3 ) 2.9
Operating result (68.1 ) (73.0 ) 4.9
Net finance result (61.1 ) 116.6 (177.7 )
Net result (0.9 ) 1.2 (2.1 )
Basic net result per share (in CHF) (1.89 ) 3.63 (5.52 )
Diluted net result per share (in CHF) (1.89 ) 3.54 (5.43 )
Net cash (used in) from operating activities (59.0 ) 118.6 (177.6 )
Cash & cash equivalents (incl. short-term time deposits) 186.9 249.1 (62.2 )
Total shareholders’ equity 176.4 235.2 (58.8 )
Number of total FTE 167.5 175.3 -7.8

Financial outlook 2024
For the full year 2024, at constant exchange rates, the Company expects total operating expenses of CHF 70-80 million, of which around CHF 8 million will be non-cash effective costs for share-based payments, IFRS pension accounting and depreciation.

Documentation

This press release, the Company’s Annual Report on Form 20-F for the year ended December 31, 2023 to be filed with the U.S. Securities and Exchange Commission (SEC), and the Company’s annual report 2023 will be made available through www.molecularpartners.com under the investor section after 9.00 pm CET (4.00 pm EST) on March 14, 2024.

Full Year 2023 Conference Call & Audio Webcast

Molecular Partners will hold a conference call and audio webcast on March 15, 1.00 pm CET (8.00 am EST).
To register for the full year 2023 conference call, please dial the following numbers approximately 10 minutes before the start of the presentation:

Participant Dial In (Toll Free): 1-866-652-5200
Participant International Dial In: 1-412-317-6060
Switzerland Toll Free: 0800-246787

Participants in the conference call will have the opportunity to ask questions after the presentation.

Audio webcast

The full year 2023 results will be webcast live and will be made available on the Company’s website under the investor section. The replay will be available for 90 days following the presentation.

On March 14, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its operational and financial results for the full year ended December 31, 2023 (Press release, Autolus, MAR 14, 2024, View Source [SID1234641179]).

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"We’re delighted to be starting 2024 in such a strong financial position; our recently announced strategic alliance with BioNTech, coupled with two equity financing transactions, raised gross proceeds of $600 million. Combined with our 2023 ending cash of $240 million, this enables us to drive the full launch and commercialization of obe-cel in r/r adult ALL and establish Autolus as a potential leader in the delivery of CAR T therapy to patients with autoimmune diseases," said Dr. Christian Itin, Chief Executive Officer of Autolus.

"2023 was a transformational year for the Company. Our lead program, obe-cel, demonstrated strong data in B-ALL in the pivotal FELIX study, we fully validated our commercial manufacturing facility, The Nucleus, to support our regulatory submissions and we submitted our first BLA for obe-cel to the United States Food and Drug Administration (FDA) in November, with a PDUFA target action date of November 16, 2024. We also just submitted an MAA to the European Medicines Agency (EMA).

"Beyond B-ALL, we see a significant opportunity for obe-cel in autoimmune disease. Our Phase 1 dose confirmation trial in refractory SLE is now open for enrollment. We believe obe-cel’s clinical profile, together with our commercial product delivery base and infrastructure, will help to drive an accelerated and differentiated expansion in autoimmune diseases and we look forward to sharing initial data from the study in late 2024.

"For now, we remain fully focused on preparing for a potential obe-cel launch and successfully transitioning Autolus to a commercial stage company. Pre-commercial and product delivery activities are well underway, and we are on track to make obe-cel available to B-ALL patients as soon as possible, following a potential approval."

Key obecabtagene autoleucel (obe-cel) updates and anticipated milestones:

Obe-cel in relapsed / refractory (r/r) adult ALL – The FELIX Study
Obe-cel BLA for r/r B-ALL submitted to the FDA in November 2023; PDUFA target action date of November 16, 2024. A marketing authorization application (MAA) to the European Medicines Agency (EMA) was just submitted and an MAA submission to the MHRA in the UK is planned for the second half of 2024.
Pooled analysis of the FELIX Phase 1b/2 study presented at ASH (Free ASH Whitepaper) in December 2023 demonstrated prolonged event free survival and low overall immunotoxicity across all cohorts in r/r B-ALL, and particularly in patients with low leukemic burden at lymphodepletion. Additionally, data from a pooled analysis from the ALLCAR19 study and FELIX Phase 1b in r/r B-ALL showed durable remissions with obe-cel as a stand-alone therapy in a subset of patients after a median follow up of >3 years. Further long-term data from the FELIX study is anticipated at medical conferences in 2024.

Obe-cel in B-cell mediated autoimmune diseases
The Phase 1 dose confirmation study in refractory systemic lupus erythematosus (SLE) patients has the first site open for enrollment; initial clinical data expected in late 2024.
Pipeline clinical trials, in collaboration with University College London (UCL), updates and anticipated milestones:

AUTO8 in Multiple Myeloma – Phase 1 MCARTY Study
AUTO8 is a next-generation product candidate for multiple myeloma, which includes two CARs for the multiple myeloma targets, BCMA and CD19. Initial data from the MCARTY Phase 1 study in multiple myeloma presented at ASH (Free ASH Whitepaper) in December 2023 showed AUTO8 was well tolerated, with responses observed in all patients. Further updates from the MCARTY study are anticipated during 2024.
AUTO6NG in Neuroblastoma – Phase 1 MAGNETO Study
AUTO6NG contains a CAR that targets GD2 alongside additional programming modules to enhance the activity and persistence. A Phase 1 clinical study in children with r/r neuroblastoma was opened for enrollment in the fourth quarter of 2023.
Post-period:

Strategic developments:

Strategic alliance with BioNTech SE

In February 2024, BioNTech and Autolus announced a strategic CAR T cell therapy collaboration to advance their pipelines and expand late-stage programs, for $50 million cash upfront and up to $582 million in potential option exercise and milestone payments. Additionally, Autolus sold $200 million of ADSs to BioNTech in a concurrent private placement financing transaction.

Overview:

BioNTech has right to utilize Autolus’ manufacturing capacity, know-how and cost-efficiencies to accelerate the planned clinical development and commercialization of BNT211
BioNTech to support launch and expansion of development program of Autolus’ lead cell therapy candidate obe-cel and will receive a royalty on net sales
BioNTech has co-commercialization options for Autolus’ AUTO1/22 and AUTO6NG programs, and an option to access a suite of Autolus target binders and cell programming technologies
Underwritten offering

In February 2024, Autolus completed an underwritten registered direct offering in the United States at a price of $6.00 per ADS, for total gross proceeds of $350 million.

Recent Operational Updates:

In March 2024, following the most recent GMP inspection by the MHRA in February 2024, The Nucleus manufacturing facility in Stevenage obtained a Manufacturer’s Importation Authorization (MIA), together with the accompanying GMP certificate. This authorization enables Autolus to manufacture products for global commercial and clinical supply at The Nucleus, effective as of March 18, 2024.
In February 2024, Autolus promoted Dr. Chris Williams to Chief Business Officer and Alex Driggs to Senior Vice President, Legal Affairs and General Counsel. Chris has been with the Company since its inception, having negotiated on behalf of UCL the spin off and formation of Autolus. Alex has been with Autolus since 2018 in the role of General Counsel.
Dr. Edgar Braendle has notified the Company that he will step down as Chief Development Officer to pursue other opportunities. Edgar will continue to advise the company during the BLA and MAA review process. Miranda Neville, SVP and obe-cel Program Leader will run the Development team.
Autolus announced the appointment of Elisabeth (Lis) Leiderman, M.D. and Robert W. Azelby to its Board of Directors. Dr. Leiderman brings extensive transactional and financial expertise, and Mr. Azelby brings more than 30 years of biopharmaceutical leadership and commercial experience to Autolus’ Board.
Scientific Publications:

In January 2024, Autolus announced the publication of a paper in ACS Chemical Biology entitled: ‘Designer small molecule control system based on Minocycline induced disruption of protein-protein interaction’ – Jha et al., ACS Chemical Biology (2024) doi:10.1021/acschembio.3c00521; [Link]
In February 2024, Autolus announced the publication of a paper in Nature Communications entitled: ‘Structure-Guided Engineering of Immunotherapies Targeting TRBC1 and TRBC2 in T Cell Malignancies’ – Ferrari et al., Nat Commun 15, 1583 (2024) doi:10.1038/s41467-024-45854-3; [Link]
In March 2024, Autolus announced the publication of a paper in Blood Cancer Journal entitled: ‘Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry – Horna et al., Blood Cancer J. 14, 34 (2024) doi: 10.1038/s41408-024-01002-0; [Link]

2024 Expected News Flow:

Obe-cel FELIX data update at ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper) & ASH (Free ASH Whitepaper) June & Dec 2024
Obe-cel Marketing Authorization Application to MHRA Second half 2024
Obe-cel U.S. FDA PDUFA target action date November 16, 2024
Obe-cel in autoimmune disease – initial data from SLE Phase 1 study Late 2024

Financial Results (Unaudited) for the Full Year Ended December 31, 2023

Cash and cash equivalents at December 31, 2023 totaled $239.6 million, as compared to $382.4 million at December 31, 2023.

Total operating expenses, net for the year ended December 31, 2023, were $179.7 million, as compared to $143.4 million, for the year ended December 31, 2022.

Research and development expenses increased from $117.4 million to $130.5 million for the year ended December 31, 2023, compared to the same period in 2022. This change was primarily due to increases in operating costs related to the Company’s new commercial manufacturing facility, contractual milestone payments and employee salaries and related costs, a decrease in our U.K. reimbursable R&D tax credits claimable through the U.K. small and medium-sized entity (SME) scheme and partially offset by decreases in clinical and manufacturing costs related to the Company’s obe-cel clinical product candidate.

In prior years, Autolus reported the R&D tax credits as income tax benefit on its statements of operations. The Company has revised its financial presentation, including the prior years, and will now present such tax credits as a reduction in research and development expense. As a result, income tax benefit has reduced by $19.5 million and $24.6 million for the years ended December 31, 2023, and 2022, respectively, with corresponding reductions in research and development expenses and total operating expenses.

General and administrative expenses increased from $31.9 million to $46.7 million for the year ended December 31, 2023, compared to the same period in 2022. This increase was primarily due to salaries and other employment-related costs driven by an increase in general and administrative headcount supporting the overall growth of the business, primarily relating to pre-commercialization activities.

Net loss attributable to ordinary shareholders was $208.4 million for the year ended December 31, 2023, compared to $148.8 million for the same period in 2022. The basic and diluted net loss per ordinary share for the year ended December 31, 2023, totaled $(1.20), compared to a basic and diluted net loss per ordinary share of $(1.57) for 2022.

Autolus estimates that, with its current cash and cash equivalents and proceeds received from the strategic alliance with BioNTech and the private placement and underwritten equity financing, it is well capitalized to drive the full launch and commercialization of obe-cel in r/r adult ALL as well as to advance its pipeline development plans, which includes providing runway to data in the first pivotal study of obe-cel in autoimmune disease.

On March 14, 2024 Anocca AB (Anocca), a leading T cell receptor-engineered T cell (TCR-T) cellular therapeutics company, and EmendoBio Inc. (EmendoBio), a nuclease discovery and gene editing therapeutics company, reported a non-exclusive licensing agreement for the use of EmendoBio’s novel OMNI-A4 nuclease to accelerate the manufacture and development of Anocca’s deep pipeline of TCR-T cell therapies for difficult-to-treat solid cancers (Press release, Anocca, MAR 14, 2024, View Source [SID1234641178]).

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"Integrating EmendoBio’s nuclease into our manufacturing process supports Anocca’s aim of generating the highest-quality cell therapy products. This next-generation gene editing system provides the precision and efficiency needed to scale out production of our growing libraries of TCR-T products in a high-precision manufacturing process. We are excited to work with EmendoBio to develop gene-edited TCR-T cell therapies as we prepare for our first clinical program targeting the KRAS driver mutation in a hard-to-treat solid cancer" said Anocca’s CEO and co-founder, Reagan Jarvis.

"This non-exclusive licensing agreement marks a significant milestone in the field of T cell therapy," said Dr. Ei Yamada, Director of EmendoBio. "Together with Anocca, we are embracing the shared vision of harnessing the potential of gene editing and cellular therapies to make a profound impact on patient outcomes. Our combined expertise will unlock novel avenues for therapeutic development and push the boundaries of what’s possible in advanced medicine."

Anocca recently received certification of GMP compliance and a manufacturing license from the Swedish regulators for their cell therapy production facility, the largest in the Nordics. EmendoBio’s technology strengthens Anocca’s manufacturing capability and provides a foundation for the ambitious goal of reaching more patients faster with personalised treatments targeting the underlying genetic drivers of hard-to-treat cancers. The licensed gene editing technology is part of EmendoBio’s portfolio of proprietary nucleases developed to be highly active and specific for cell therapy applications.

Anocca’s and Emendo’s commitment to innovation and scientific excellence sets the stage for a promising future in T cell therapies. The agreement not only underscores the significance of collaborative efforts in the biotechnology sector but also reinforces both companies’ dedication to improving global healthcare outcomes.

On March 14, 2024 Cellipont Bioservices, a leading cell therapy Contract Development and Manufacturing Organization (CDMO), and Wugen, Inc., a clinical-stage biotechnology company developing allogeneic, off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported the signing of an agreement for the manufacturing of their CAR-T cell therapies (Press release, Wugen, MAR 14, 2024, View Source [SID1234641174]).

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Under the agreement, Cellipont Bioservices will be providing the technology transfer and production of Wugen’s allogeneic CAR-T cell therapies at their new purpose-built 76,000 sq. ft. manufacturing facility.

Wugen is developing the next generation of off-the-shelf memory natural killer (NK) and CAR-T cell therapies for cancer. The company’s investigational cell therapies originate from healthy donors and are further engineered to enhance their function of eliminating cancer cells. Their NK cell and CAR-T immuno-oncology therapies address the needs of patients with solid tumors, acute myeloid leukemia (AML) and T-cell malignancies.

"We are excited to collaborate with Cellipont Bioservices, leveraging their expertise in cell therapy manufacturing to carry out our mission of bringing innovative CAR-T cell therapies to patients in need. This new partnership helps enable Wugen to achieve our mission to help patients with hematological malignancies with off-the-shelf cell therapies," said Kumar Srinivasan, Ph.D., MBA, president and CEO of Wugen.

"We are thrilled to partner with Wugen, Inc. in advancing their groundbreaking CAR-T cell therapies. This collaboration underscores our commitment to driving innovation and accelerating the development of life-saving treatments for patients worldwide," said Edwin Beale, CCO of Cellipont.

On March 14, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided an overview of recent developments (Press release, UroGen Pharma, MAR 14, 2024, View Source [SID1234641173]).

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"In 2023, UroGen achieved important operational and clinical milestones, setting us up for further success in the coming years," said Liz Barrett, President and Chief Executive Officer of UroGen. "The Phase 3 ATLAS and ENVISION trials both produced meaningful and unprecedented results underscoring the potential of UGN-102 to fundamentally change the way patients with low-grade intermediate-risk non-muscle invasive bladder cancer are treated. We look forward to reporting the 12-month duration of response data from ENVISION in the second quarter of 2024 and to completing submission of an NDA in September of this year. UGN-102 has the potential to address a more than $3 billion market opportunity and, if approved, has the potential to be transformative for our company. JELMYTO continues to show double digit growth with patient and physician adoption expected to continue to increase."

2023 and Recent Business Highlights:

UGN-102 (mitomycin) for intravesical solution:

In January 2024, UroGen initiated submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The first part of the submission was the Chemistry, Manufacturing and Controls (CMC) sections. The FDA indicated that evaluation of duration of complete response at 12-months from the pivotal ENVISION trial will be sufficient to support submission of the NDA. The company plans to complete the submission in September 2024 with a potential FDA decision as early as the first quarter of 2025.
Positive top-line data from ATLAS Phase 3 clinical trial highlighting UGN-102 as non-surgical treatment option for LG-IR-NMIBC published in The Journal of Urology.
JELMYTO (mitomycin) for pyelocalyceal solution in low-grade upper tract urothelial cancer (LG-UTUC):

Generated annual net product revenue of $82.7 million in 2023, compared with $64.4 million in 2022 in representing ~28% annual growth.
Patient enrollment forms, new patient starts, and total doses each grew approximately 25% year-over-year. First-time writers, activated sites and repeat accounts also continue to grow.
A retrospective study investigated whether patients with higher-volume low-grade disease could achieve disease-free status using partial ablation or biopsy before JELMYTO treatment during initial ureteroscopy. The study found no significant difference in disease-free rates between complete ablation (78.6%), partial ablation (57.6%), or biopsy-only (66.7%) groups during initial ureteroscopy. Tumor size prior to JELMYTO induction also showed no significant impact on disease-free rates. The study aimed to find alternatives to nephroureterectomy for preserving kidney function and to assess JELMYTO’s efficacy in managing larger volume disease. Findings from the study were published online in Urologic Oncology: Seminars and Original Investigations online.
Next-generation novel mitomycin-based formulation for urothelial cancers

In January 2024, UroGen announced a license and supply agreement with medac GmbH to develop a next-generation novel mitomycin-based formulation for urothelial cancers. UGN-103 and UGN-104 combine UroGen’s RTGel technology with medac’s licensed mitomycin formulation. The agreement and development program potentially allow UroGen to extend the patent protection on its urothelial cancer franchise. medac has intellectual property protection for its mitomycin formulation expected to last until June 2035 and UroGen has pending U.S. patent applications which may provide protection until December 2041.
UroGen plans to initiate Phase 3 studies to explore the safety and efficacy of UGN-103 and UGN-104 in LG-IR-NMIBC and LG-UTUC, respectively, in 2024.
Up to $100 Million Letter of Credit Facility with Funds Managed by Pharmakon

Announced signing of a restructured loan agreement with Pharmakon Advisors providing UroGen additional funding of up to $100 million. Under the terms of the restructured agreement, the interest rate on the previously funded $100 million loan is reduced, and the initiation of the payback period will be delayed following UGN-102 approval. The restructured agreement also includes a credit facility of up to $100 million. As part of the agreement, UroGen is required to draw down on the first tranche of $25 million of the credit facility by September 30, 2024, and will have the option to access as much as an additional $75 million following UGN-102 approval.
Fourth Quarter and Full Year 2023 Financial Results

JELMYTO Revenue: UroGen reported JELMYTO net product revenues of $23.5 million in the fourth quarter of 2023, compared to $18.1 million for the same period in 2022. Net JELMYTO product revenue for the full year 2023 was $82.7 million, compared to $64.4 million in 2022. Despite strong unit growth, full year 2023 net revenues were impacted by higher than forecast 340B chargebacks and first time estimated Medicare refunds for discarded drug, offset by non-patient purchases.

R&D Expense: Research and development expenses for the fourth quarter of 2023 were $11.3 million, including non-cash share-based compensation expense of $0.5 million as compared to $14.5 million, including non-cash share-based compensation expense of $0.6 million, for the same period in 2022. Research and development expenses for the full year 2023 were $45.6 million, including non-cash share-based compensation expense of $1.9 million as compared to $52.9 million, including non-cash share-based compensation expense of $2.6 million, in 2022.

SG&A Expense: Selling, general and administrative expenses for the fourth quarter of 2023 were $24.6 million, including non-cash share-based compensation expense of $2.1 million. This compares to $21.6 million, including non-cash share-based compensation expense of $1.8 million, for the same period in 2022. Selling, general and administrative expenses for the full year 2023 were $93.3 million, including non-cash share-based compensation expense of $7.4 million. This compares to $82.8 million, including non-cash share-based compensation expense of $8.0 million, in 2022.

Financing on Prepaid Forward Obligation: UroGen reported non-cash financing expense related to the prepaid forward obligation to RTW Investments of $5.5 million in the fourth quarter of 2023, compared to $5.1 million in the same period in 2022. Non-cash financing expense related to the RTW Investments obligation was $21.6 million for the full year 2023, compared to $21.6 million in 2022. The rate applied to cash payments incurred in 2023 is 13% based on global JELMYTO net product sales of $82.7 million in 2023.

Interest Expense on Long-Term Debt: Interest expense related to the $100 million term loan facility with funds managed by Pharmakon Advisors was $3.6 million and $14.7 million, respectively for the fourth quarter and full year 2023, compared to $3.2 million and $8.4 million in the same periods in 2022. The higher amount in 2023 was a result of interest expense for four full quarters in 2023, whereas the first and second tranches of the loan were funded in March 2022 and December 2022, respectively.

Net Loss: UroGen reported a net loss of $26.0 million or ($0.72) per basic and diluted share in the fourth quarter of 2023 compared with a net loss of $28.9 million or ($1.25) per basic and diluted share in the same period in 2022. Net loss was $102.2 million or ($3.55) per basic and diluted share in the full year 2023 compared with a net loss of $109.8 million or ($4.81) per basic and diluted share in 2022.

Cash & Cash Equivalents: As of December 31, 2023, cash, cash equivalents and marketable securities totaled $141.5 million.

2024 Revenue, Operating Expense and RTW Expense Guidance: The Company anticipates full year 2024 net product revenues from JELMYTO to be in the range of $95 to $102 million. Increased discounts related to Medicare refunds for discarded drugs and 340B purchases will further impact net revenues in 2024. The Company also expects full year 2024 operating expenses in the range of $175 to $185 million, including non-cash share-based compensation expense of $6 to $11 million, subject to market conditions. The Company also reiterates anticipated full year 2024 non-cash financing expense related to the prepaid obligation to RTW Investments in the range of $21 to $26 million. Of this amount approximately $12.4 to $13.3 million is expected to be in cash.

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 UroGen’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.

UROGEN PHARMA LTD.

SELECTED CONSOLIDATED BALANCE SHEETS

(U.S. dollars in thousands)

(Unaudited)

December 31,
2023

December 31,
2022

Cash and cash equivalents and marketable securities

$

141,469

$

99,963

Total assets

$

178,311

$

135,619

Total liabilities

$

243,523

$

224,980

Total shareholders’ deficit

$

(65,212

)

$

(89,361

)

UROGEN PHARMA LTD.

CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS

(U.S. dollars in thousands, except share and per share data)

(Unaudited)

Three months ended
December 31,
(Unaudited)

Year ended

December 31,

2023

2022

2023

2022

Revenue1

$

23,530

$

18,092

$

82,713

$

64,357

Cost of revenue

2,286

2,263

9,361

7,654

Gross profit

21,244

15,829

73,352

56,703

Operating expenses:

Research and development expenses

11,302

14,477

45,614

52,906

Selling, general and administrative expenses

24,551

21,634

93,274

82,838

Total operating expenses

35,853

36,111

138,888

135,744

Operating loss

(14,609

)

(20,282

)

(65,536

)

(79,041

)

Financing on prepaid forward obligation

(5,505

)

(5,081

)

(21,552

)

(21,559

)

Interest expense on long-term debt

(3,586

)

(3,223

)

(14,715

)

(8,438

)

Interest and other income, net

1,538

406

3,479

1,010

Loss before income taxes

$

(22,162

)

$

(28,180

)

$

(98,324

)

$

(108,028

)

Income tax expense

(3,854

)

(689

)

(3,920

)

(1,775

)

Net loss

$

(26,016

)

$

(28,869

)

$

(102,244

)

$

(109,783

)

Net loss per ordinary share basic and diluted

$

(0.72

)

$

(1.25

)

$

(3.55

)

$

(4.81

)

Weighted average shares outstanding, basic and diluted

36,153,634

23,088,891

28,834,303

22,806,812

1.

2023 full-year JELMYTO net revenues include gross-to-net unfavorability driven by higher 340B chargebacks and estimated Medicare refunds for discarded drugs, offset by $4.4 million in CREATES Act sales, of which $2.4 million was realized in Q4 2023.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for the treatment of adult patients with LG-UTUC. It is recommended for primary treatment of biopsy-proven LG-UTUC in patients deemed appropriate candidates for renal-sparing therapy. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

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 innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of low-grade, intermediate-risk, non-muscle invasive bladder cancer (LG-IR-NMIBC). Utilizing UroGen’s proprietary RTGel technology, a 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 in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates completing its NDA submission for UGN-102 in September with a potential FDA decision as early as the first quarter of 2025.