On August 13, 2024 XOMA Royalty Corporation (NASDAQ: XOMA), the biotech royalty aggregator, reported its second quarter 2024 financial results and highlighted recent activities (Press release, Xoma, AUG 13, 2024, View Source [SID1234645824]).

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 second quarter was marked by pipeline progress, the realization of several cash milestones, the addition of three commercial or late-stage programs, and the acquisition of Kinnate Pharmaceuticals," stated Owen Hughes, Chief Executive Officer of XOMA Royalty. "Most important, children suffering from relapsed or refractory low-grade glioma (pLGG) have a new option with the approval of Day One’s OJEMDA, which is now our fifth commercial royalty. And finally, with a robust cash position in hand, we look to further solidify our foundation for future growth via a disciplined approach to capital deployment."

Key Second Quarter Events

Partner

Event

Day One Biopharmaceuticals

The U.S. Food and Drug Administration (FDA) approved Day One’s OJEMDA (tovorafenib) for use in patients with pediatric low-grade glioma (pLGG). XOMA Royalty earned a $9.0 million milestone upon the approval and recorded $0.4 million in income resulting from OJEMDA sales in the second quarter of 2024. In addition, XOMA Royalty received an $8.1 million payment related to Day One’s sale of its priority review voucher.
Daré Bioscience

XOMA Royalty added economic interests to three best- or first-in-category assets to its portfolio. XACIATO vaginal gel 2% is commercially available and marketed by Organon. Bayer holds the U.S. rights to commercialize Ovaprene, a hormone-free monthly intravaginal contraceptive, currently in Phase 3 clinical trials. XOMA Royalty also acquired a synthetic royalty in Sildenafil Cream, 3.6%, a Phase 3-ready asset for female sexual arousal disorder. Daré recently published the efficacy results from its Phase 2b study of Sildenafil Cream, 3.6% in the publication Obstetrics & Gynecology.
Rezolute

RZ358—Dosed first patient in its Phase 3 trial of RZ358; XOMA Royalty earned a $5.0 million milestone associated with the event.

Presented Phase 2 RIZE study sub-analysis at the 2024 Pediatric Endocrine Society Annual Meeting.

RZ402—Presented positive topline results from its Phase 2 proof-of-concept study of RZ402 in patients with diabetic macular edema (DME). The data indicate RZ402 could be an effective oral therapy for patients with DME prior to anti-VEGF injections. Rezolute announced its intention to seek a partner for the next stage of development and future commercialization activities.

Takeda

Announced late-breaking data from Takeda’s Phase 2b study of mezagitamab demonstrating its potential to transform the treatment of primary immune thrombocytopenia1. In the study, patients receiving mezagitamab showed rapid and sustained increases in platelet counts that persisted 8 weeks after the last dose through to week 162.
Kinnate Pharmaceuticals

XOMA Royalty added several potential royalty streams, as well as more than $9.5 million to its cash balance as it completed the acquisition of Kinnate Pharmaceuticals.
LadRx

Regained development and commercialization rights to aldoxorubicin from ImmunityBio. XOMA Royalty is eligible to receive a low single-digit percent royalty on future sales of aldoxorubicin and a portion of any future milestone payments LadRx receives.

1
View Source

2
Kuter D, Pulanic D, et al. Safety, tolerability, and efficacy of mezagitamab (TAK-079) in chronic or persistent primary immune thrombocytopenia: Interim results from a phase 2, randomized, double-blind, placebo-controlled study. In: International Society on Thrombosis and Haemostasis (ISTH) Congress; June 22-26, 2024; Bangkok, Thailand. Abstract LB 01.1.

Subsequent Events
Partner

Event

Zevra Therapeutics

FDA convened a meeting of its Genetic Metabolic Diseases Advisory Committee (GeMDAC) on August 2, 2024, to discuss the New Drug Application (NDA) for arimoclomol as a treatment in adults and pediatric patients 2 years and older with Niemann-Pick Disease Type C (NPC). The GeMDAC Advisory Committee voted favorably (11 yes, 5 no) that the data support that arimoclomol is effective in the treatment of patients with NPC. The Committee’s recommendation will be considered by FDA as it completes its independent review of the arimoclomol NDA; however, the feedback from the GeMDAC is not binding upon the Agency.
Anticipated 2024 Events of Note
Partner

Event

Zevra Therapeutics

September 21, 2024 – FDA PDUFA action date for arimoclomol NDA
Takeda

In its press release dated June 22, 2024, Takeda announced plans to initiate a global Phase 3 trial of mezagitamab in ITP in the second half of fiscal year 2024.1
Second Quarter 2024 Financial Results

XOMA Royalty recorded total income and revenues of $11.1 million for the second quarter of 2024, which included $4.9 million in estimated income associated with two commercial products in our portfolio, $0.5 million in income from the $9.0 million milestone payment received from the FDA approval of OJEMDA, and $5.0 million in revenue from contracts with customers related to a milestone payment from Rezolute. In the second quarter of 2023, XOMA Royalty reported total income and revenue of $1.7 million, which included $1.1 million of revenue from contracts with customers related to a milestone earned from Janssen.

Research and development (R&D) expenses were $1.2 million in the second quarter of 2024, reflecting the ongoing clinical activities related to Kinnate’s Phase 1 clinical trial of KIN-3248, which XOMA Royalty assumed upon completing the Kinnate merger. The Company expects to incur additional R&D costs as this trial winds down in the second half of 2024. R&D expenses in the second quarter of 2023 were $39,000.

General and administrative ("G&A") expenses were $11.0 million for the second quarter of 2024 compared with $5.8 million in the second quarter of 2023. The increase of $5.2 million was driven primarily by expenses associated with our acquisition of Kinnate, which included $3.6 million in severance costs paid to Kinnate senior leadership, $1.0 million in consulting fees, and $0.8 million in other administrative costs.

In the second quarter of 2024, as a result of communications with Aronora, XOMA Royalty evaluated the status of the partnered programs for potential impairment and recorded a one-time, non-cash impairment charge of $9.0 million and a reduction of royalty receivables of $9.0 million associated with Aronora. In 2023, as a result of the announcement by Bioasis to suspend its operations and the termination of its research collaboration and license agreement with Chiesi, XOMA Royalty recorded a one-time, non-cash impairment charge of $1.6 million and a reduction of $1.6 million under long-term royalty receivables in the second quarter of 2023.

In the second quarters of 2024 and 2023, G&A expenses included $2.7 million and $2.2 million, respectively, in non-cash stock-based compensation expenses.

XOMA Royalty recorded a $19.3 million gain on the acquisition of Kinnate in the second quarter of 2024 due to the fair value of net assets that exceeded total purchase consideration.

During the second quarter of 2024, XOMA Royalty recognized an $8.1 million change in the fair value of an embedded derivative related to the payment of $8.1 million for the sale of a priority review voucher by Day One that was earned pursuant to XOMA Royalty’s RPA with Viracta.

Interest expense in the second quarter of 2024 was $3.4 million, representing interest related to the Blue Owl Loan established in December 2023.

The Company reported total other income, net, of $2.1 million in the second quarter of 2024, as compared to total other income, net, of $0.6 million in the corresponding period of 2023. The $1.5 million increase reflects a $1.2 million increase in investment income due to higher cash balances and higher market interest rates on our investments, as well as the change in the market price of Rezolute’s common stock.

Net income for the second quarter of 2024 was $16.0 million, compared to a net loss of $5.4 million for the second quarter of 2023.

On June 30, 2024, XOMA Royalty had cash and cash equivalents of $149.9 million (including $6.0 million in restricted cash). On December 31, 2023, XOMA Royalty had cash and cash equivalents of $159.6 million (including $6.3 million in restricted cash). During the second quarter of 2024, XOMA Royalty received $22.6 million in cash from royalty and milestone payments and deployed $22.0 million to acquire new royalty and milestone economic interests. Net cash used in operating activities during the quarter was $2.2 million. On July 15, 2024, the Company paid a total of $1.4 million in cash dividends on the 8.625% Series A Cumulative Perpetual Preferred Stock (Nasdaq: XOMAP) and the 8.375% Series B Cumulative Perpetual Preferred Stock (Nasdaq: XOMAO).

On August 13, 2024 Immatics N.V. (NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported a business update and announced financial results for the quarter ended June 30, 2024 (Press release, Immatics, AUG 13, 2024, View Source [SID1234645809]).

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!

"It is an exciting time for Immatics as we prepare to reach several major clinical milestones in the second half of the year. Starting with the presentation of the first clinical data on our TCR Bispecific, TCER IMA401, at ESMO (Free ESMO Whitepaper), followed by further data updates from our cell therapy pipeline and the initiation of the IMA203 registration-enabling clinical trial, we look forward to the continued advancement of our product candidates in the coming months," said Harpreet Singh, Ph.D., CEO and Co-Founder of Immatics. "Patients with advanced solid tumors are in need of transformative therapies that make a meaningful difference in their quality of life. With each clinical milestone we reach, we move one step closer to making an impact in the lives of these patients."

Second Quarter 2024 and Subsequent Company Progress

ACTengine Cell Therapy Program

ACTengine IMA203 and IMA203CD8 (GEN2) monotherapy

On May 14, 2024, Immatics provided a data update on IMA203 monotherapy targeting PRAME from the ongoing Phase 1 trial at the recommended Phase 2 dose (RP2D, 1 to 10 billion total TCR-T cells) in 30 heavily pretreated metastatic melanoma patients evaluable for efficacy.

As of the data cut-off on April 25, 2024, treatment with IMA203 monotherapy in the efficacy population has demonstrated a confirmed objective response rate (cORR) of 55% (16/29), a disease control rate of 90% (27/30) and tumor shrinkage in 87% (26/30) of patients.

Median duration of response (mDOR) was 13.5 months (min 1.2+, max 21.5+ months) including 11 of 16 confirmed objective responses ongoing at data cut-off and longest duration of response ongoing at >21 months after infusion.

Confirmed response rates are similar across all melanoma subtypes (56% (9/16) in cutaneous melanoma and 54% (7/13) in other melanoma subtypes). IMA203 has exhibited a favorable tolerability profile (N=65 patients across all dose levels and all tumor types).

The next data update, which will include translational and clinical data for IMA203, as well as further details on the clinical trial design for the planned IMA203 Phase 2/3 study, will be presented in 2H 2024 at a medical conference.

Immatics is continuing dose escalation of IMA203CD8 (GEN2) with the goal of defining the optimal dose for further development. The next data update for IMA203CD8 (GEN2) is planned for 2H 2024 with a focus on continued dose escalation data in melanoma patients. In addition to treating melanoma patients, Immatics has also started to expand its clinical footprint outside of melanoma to address a broader patient population with a particular focus on ovarian and uterine cancers.

TCR Bispecifics Programs

Immatics’ T cell engaging receptor (TCER) candidates are next-generation, half-life extended TCR Bispecific molecules. They are designed to maximize efficacy while minimizing toxicities and provide a patient-convenient dosing schedule through the proprietary format consisting of a high-affinity TCR domain against the tumor target and a low-affinity T cell recruiter binding to the T cell.

Upcoming milestones for Immatics’ clinical TCER pipeline

Martin Wermke, M.D. will present the first clinical data from Immatics’ IMA401 (MAGEA4/8) at the ESMO (Free ESMO Whitepaper) Congress during an oral presentation titled, Initial safety, pharmacokinetics, and anti-tumor activity data of TCER IMA401, a MAGEA4/8-directed half-life extended TCR Bispecific, in Phase 1 dose escalation, on September 16, 2024, at 11:25 CEST.

Data from approximately 30 patients from the dose escalation phase will be presented. Key objectives include: (1) Demonstrating tolerability of the novel, next-generation, half-life extended TCR Bispecifics format; (2) optimizing dosing schedule to a less frequent regimen during dose escalation, based on pharmacokinetics data; and (3) demonstrating initial clinical anti-tumor activity.

IMA402 (PRAME) data are planned to be announced later in 2H 2024 and will include data from at least 15 patients in early stages of dose escalation across multiple solid cancers, but initially focused on melanoma.

TCER IMA401 (MAGEA4/8)

The Phase 1 dose escalation basket trial to evaluate safety, tolerability and initial anti-tumor activity of TCER IMA401 in patients with recurrent and/or refractory solid tumors is ongoing. IMA401 targets an HLA-A*02:01-presented peptide that occurs identically in two different proteins, MAGEA4 and MAGEA8. This target peptide has been selected based on natural expression in native solid tumors at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT is >5x higher than for a MAGEA4 peptide target used in other clinical trials). MAGEA4 and MAGEA8 are expressed in multiple solid cancers including lung cancer, head and neck cancer, melanoma, ovarian cancer, sarcoma and others.

IMA401 is being developed in collaboration with Bristol Myers Squibb.

TCER IMA402 (PRAME)

Immatics initiated the Phase 1/2 trial investigating the Company’s fully owned TCER candidate IMA402 in patients with recurrent and/or refractory solid tumors in August 2023. Initial focus indications are ovarian cancer, lung cancer, uterine cancer and cutaneous and uveal melanoma, among others. IMA402 targets an HLA-A*02:01-presented peptide derived from the tumor antigen PRAME. This target peptide has been selected based on natural expression in native solid primary tumors and metastases at particularly high target density (peptide copy number per tumor cell identified by Immatics’ proprietary quantitative mass spectrometry engine XPRESIDENT).

Corporate Development

In July 2024, Alise Reicin, M.D., was appointed to Immatics’ Board of Directors as the Company is advancing its pipeline of TCR-based cell therapy and bispecific product candidates into the next phase of development. Dr. Reicin brings extensive experience in early- and late-stage clinical development and has led the successful development of multiple important new therapies, including Keytruda.

Second Quarter 2024 Financial Results

Cash Position: Cash and cash equivalents as well as other financial assets total €531.1 million ($568.5 million1) as of June 30, 2024, compared to €425.9 million ($455.9 million1) as of December 31, 2023. The increase is mainly due to the public offering in January 2024, partly offset by ongoing research and development activities. The Company projects a cash runway into 2027.

Revenue: Total revenue, consisting of revenue from collaboration agreements, was €18.8 million ($20.1 million1) for the three months ended June 30, 2024, compared to €22.4 million ($24.0 million1) for the three months ended June 30, 2023. The decrease is mainly the result of a one-time revenue of €13.7 million associated with an opt-in payment by BMS during the three months ended June 30, 2023.

Research and Development Expenses: R&D expenses were €35.2 million ($37.7 million1) for the three months ended June 30, 2024, compared to €27.3 million ($29.2 million1) for the three months ended June 30, 2023. The increase mainly resulted from costs associated with the advancement of the clinical pipeline candidates.

General and Administrative Expenses: G&A expenses were €10.1 million ($10.8 million1) for the three months ended June 30, 2024, compared to €9.4 million ($10.1 million1) for the three months ended June 30, 2023.

Net Profit and Loss: Net loss was €18.0 million ($19.3 million1) for the three months ended June 30, 2024, compared to a net loss of €24.6 million ($26.3 million1) for the three months ended June 30, 2023. The decrease in net loss despite decreased revenue and increased operating expenses is driven by an increased financial result.

Full financial statements can be found in the 6-K filed with the Securities and Exchange Commission (SEC) on August 13, 2024, and published on the SEC website under www.sec.gov.

Upcoming Investor Conferences

Jefferies London Healthcare Conference, London, United Kingdom – November 19 – 21, 2024

To see the full list of events and presentations, visit www.investors.immatics.com/events-presentations.

On August 13, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported financial results for the six months ended June 30, 2024, and provided a corporate update (Press release, MediGene, AUG 13, 2024, View Source [SID1234645825]).

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 half-year 2024 earnings report can be found on the website: View Source

Select Half-Year 2024 Financial Results:

Revenues in the reporting period amounted to EUR 4.5 million, an increase of 46% compared to EUR 3.1 million in the first half of 2023. This increase compared to the first half of 2023 is due to the reversal of the remaining contractual liability to Hongsheng Sciences HK Limited (EUR 1.5 million) following the termination of the partnership.

General & administrative expenses decreased by 5% to EUR 4.1 million in the first half of 2024 (6M 2023: EUR 4.3 million including selling expenses), in particular due to lower personnel expenses.

Research and development expenses increased by 21% to EUR 6.3 million in the first half of 2024 (6M 2023: EUR 5.2 million). The reason for the increase is the focus on the development of TCR-T therapies (MDG1015, MDG2011 and MDG2021) for the treatment of solid tumors and preparatory activities for clinical trials (MDG1015).

The net result of the first half of 2024 improved by EUR 0.3 million to EUR -6.7 million compared to the first half of 2023 (6M 2023: EUR -7.0 million).

As of June 30, 2024, cash and cash equivalents amounted to EUR 14.0 million (December 31, 2023: EUR 16.7 million including time deposits). There were no open credit lines.

"In the first half of 2024, we are delighted to have again delivered on all the elements of our corporate strategy. We significantly advanced our End-to-End Platform, adding new technologies such as our innovative Interferon-gamma (IFNγ) Biosensor and our novel TCR-specific antigen-antibody combination technology, UniTope & TraCR. We advanced our lead program MDG1015 towards a first-in-human clinical trial, which is expected to start by the end of 2024 subject to additional financing," said Selwyn Ho, Chief Executive Officer of Medigene." We also successfully closed an oversubscribed capital raise with subscription rights resulting in gross proceeds of approximately EUR 5.9 million, which allowed us to extend our cash runway into July 2025. In addition, we announced our new strategic partnership with WuXi Biologics last week, expanding the ability to apply Medigene’s TCRs into new modalities, such as TCR-guided T cell engagers, to create additional value beyond TCR-T therapies for both, patients and our shareholders."

Financial Guidance 2024:

Performance in the first half of 2024 was in line with the Executive Management Board’s expectations.

On May 8, 2024, the Company reported that it had successfully completed an oversubscribed capital raise with gross proceeds of approximately EUR 5.9 million. The Company therefore amended its guidance and extended its cash runway into July 2025 (initial 2024 guidance: cash runway into April 2025).

Research and development costs were also amended and are expected to increase from prior estimates of EUR 11.0 to 13.0 million to EUR 11.5 to 13.5 million in 2024 to support additional activities enabling first patient enrollment for MDG1015 Phase 1 clinical trial by the end of 2024, subject to further financing.

The Company maintained its guidance on expected revenues to be between EUR 9.0 and 11.0 million (unchanged) in 2024.

These projections include potential future milestone payments from existing partnerships that are highly likely to materialize(see Annual Report 2023). They do not include potential milestone payments from or future/new partnerships or transactions as the occurrence of such payments or their timing and size largely depend on third parties and cannot be controlled or influenced by Medigene.

Program development highlights:

MDG1015: MDG1015 is a first-in-class, third generation T cell receptor engineered T cell (TCR-T) therapy targeting NY-ESO-1/LAGE-1a (New York esophageal squamous cell carcinoma 1 / L Antigen Family Member-1a), armored and enhanced by the costimulatory switch protein PD1-41BB and targeting HLA-A*02 (HLA, human leukocyte antigen). Pre-clinical data presented in 2024 at the AACR (Free AACR Whitepaper) and CHI conferences demonstrated the clear potential of MDG1015 to improve clinical outcomes in solid tumors with the innovative approach of combining a 3S (specific, sensitive and safe) TCR with the Company’s PD1-41BB costimulatory switch protein technology as well as an optimized drug product composition.

Following positive EU and US preliminary regulatory interactions, the Company remains on track for IND-filing in Q3 and CTA-filing in Q4 2024. Subject to financing, the Company expects to initiate a first in-human trial for MDG1015 by the end of 2024.

MDG2011: MDG2011 is a potential best-in-class third generation TCR-T therapy targeting KRAS G12V (HLA-A*11), further armored and enhanced by the PD1-41BB costimulatory switch protein. Pre-clinical data on MDG2011 was presented at the International Neoantigen Summit and the CIMT (Free CIMT Whitepaper) Annual Meeting in 2024.

MDG2021 MDG2021is the second candidate within the KRAS library targeting KRAS G12D (HLA-A*11) for which the Company announced the lead selection in June 2024.

MDG2012: The lead selection for the Company’s third announced KRAS-targeted program MDG2012,KRAS G12V (HLA-A*03), is expected in 2025.

Corporate development highlights:

In May 2024, Medigene successfully closed an oversubscribed capital raise with subscription rights resulting in gross proceeds of approximately EUR 5.9 million.

Subsequent to the quarter on August 8, 2024, the Company announced it has entered into a three-year, multi-target strategic partnership to design and co-research T cell receptor (TCR)-guided T Cell Engagers (TCR-TCEs) for the treatment of difficult-to-treat tumors with WuXi Biologics. The collaboration combines the respective expertise of each company with Medigene’s 3S TCR generation and characterization capabilities and WuXi Biologics’ unique anti-CD3 mAb, its industry-leading TCE platform and proprietary bispecific antibody platform WuXiBody. The companies aim to co-research TCR-TCE constructs, which will be owned by both cooperation partners with options to Medigene to further advance their development.

Expansion of patent portfolio:

The advancement of its End-to-End Platform allowed the Company to extend and strengthen its patent portfolio with new technologies as well as to expand existing patents into additional jurisdictions, such as the submission of three patents to the European Patent Office protecting the Company’s innovative Interferon-gamma (IFNγ) Biosensor and its novel T cell receptor (TCR)-specific antigen-antibody combination technology, UniTope & TraCR, the patent grant by the European Patent Office and Japan Patent Office protecting the inducible Medigene T cell receptor (iM-TCR) technology as well as the patent grant by the European Patent Office protecting the Company’s TCR targeting NY-ESO-1 and LAGE 1a. As of June 30, 2024, the patent portfolio consisted of 97 issued patents and 124 pending patent applications (December 31, 2023: 28 patent families, 112 issued patents and 131 pending patent applications).

Conference call and webcast:

The Company will host a conference call today, August 14, at 3:30 pm CEST / 9:30 am EDT. In addition to the financial results for the first six months of 2024, Medigene will provide a corporate update including its new partnership with WuXi Biologics (see press release on Aug 8, 2024).

Full details for the conference call and webcast are as follows:

Date Wednesday, August 14, 2024
Time 3:30 pm CEST (9:30 am EDT)
Conference call Registration conference call here
Webcast Join the live webcast here
Participants may pre-register and will receive dedicated dial-in details to easily and quickly access the call with the above registration link for the conference call.
Please dial in 10 minutes ahead of time to ensure a timely start of the conference call.
Following the call, an archived webcast will be accessible on the Investors & Media section on Medigene’s website: View Source

On August 13, 2024, Inovio Pharmaceuticals, Inc. (the "Company") entered into an Equity Distribution Agreement (the "Sales Agreement") with Oppenheimer & Co. Inc., as sales agent (the "Sales Agent") under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.001 per share (the "Common Stock"), through the Sales Agent (Filing, 8-K, Inovio, AUG 13, 2024, View Source [SID1234645810]).

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!

Pursuant to the Sales Agreement, sales of the Common Stock, if any, will be made under the Company’s previously filed and effective Registration Statement on Form S-3 (File No. 333-275445). The Company will file a prospectus supplement for the offer and sale of its Common Stock pursuant to the Sales Agreement having an aggregate offering price of up to $60,000,000.

Subject to the terms and conditions of the Sales Agreement, the Sales Agent may sell the Common Stock by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415(a)(4) of the Securities Act of 1933, as amended. The Sales Agent will use commercially reasonable efforts to sell the Common Stock from time to time, based upon instructions from the Company, including any price, time or size limits or other customary parameters or conditions the Company may impose. The Company will pay the Sales Agent a commission of up to three percent (3.0%) of the gross sales proceeds of any Common Stock sold through the Sales Agent under the Sales Agreement, and the Company has provided the Sales Agent with certain indemnification rights. The Company also will reimburse the Sales Agent for certain specified expenses in connection with entering into the Sales Agreement. The Company has no obligation to sell any of the Common Stock under the Sales Agreement and may at any time and from time to time suspend the offering of the Common Stock under the Sales Agreement.

The foregoing description of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K.

The legal opinion of Cooley LLP relating to the validity of the Common Stock being offered pursuant to the Sales Agreement is filed as Exhibit 5.1 to this Current Report on Form 8-K.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On August 13, 2024 AstraZeneca reported that Imfinzi (durvalumab) and Lynparza (olaparib) have been approved in the European Union (EU) as treatment for certain patients with primary advanced or recurrent endometrial cancer (Press release, AstraZeneca, AUG 13, 2024, View Source [SID1234645826]). Imfinzi plus chemotherapy as 1st-line treatment followed by Lynparza and Imfinzi has been approved for patients with mismatch repair proficient (pMMR) disease. Imfinzi plus chemotherapy followed by Imfinzi alone has been approved for patients with mismatch repair deficient (dMMR) disease.

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 approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on a prespecified exploratory subgroup analysis by mismatch repair (MMR) status from the DUO-E Phase III trial, which was published in the Journal of Clinical Oncology.

In the trial, the Lynparza and Imfinzi regimen reduced the risk of disease progression or death for patients with pMMR disease by 43% (median 15.0 months versus 9.7 months, hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.44-0.73) versus the control arm.1 The Imfinzi regimen reduced the risk of disease progression or death among patients with dMMR disease by 58% (median not reached versus 7.0 months, HR 0.42; 95% CI 0.22-0.80) versus the control arm.1

Els Van Nieuwenhuysen, Gynaecological Oncologist at the UZ Leuven, Belgium and DUO-E trial investigator, said: "This approval is welcome news for patients with advanced or recurrent endometrial cancer in Europe, especially those with mismatch repair proficient disease who have limited options. The olaparib and durvalumab as well as the durvalumab regimens now have the potential to improve outcomes for all patients in this setting in Europe, regardless of mismatch repair status."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "This approval of Imfinzi and Lynparza regimens marks the first-ever approval for a combination of an immunotherapy and PARP inhibitor in endometrial cancer and a major step forward for patients. In Europe, endometrial cancer is the fourth most common cancer in women, and until now, the 70 to 80 per cent of patients who have mismatch repair proficient disease have had few available treatment options."

The safety profiles of both regimens were generally manageable, well-tolerated and broadly consistent with the known profiles of the individual agents.1,2,3

Regulatory submissions for Imfinzi and Lynparza are currently under review in Japan and several other countries based on the DUO-E trial. Imfinzi plus chemotherapy was recently approved for dMMR patients with primary advanced or recurrent endometrial cancer in the US.

Notes

Endometrial cancer
Endometrial cancer is a highly heterogeneous disease that originates in the tissue lining of the uterus and is most common in women who have already been through menopause, with the average age at diagnosis being over 60 years old.4-7

The majority of patients with endometrial cancer are diagnosed at an early stage of disease, where the cancer is confined to the uterus.8 They are typically treated with surgery and/or radiation, and the five-year survival rate is high (approximately 80-90%).9 Patients with advanced disease (Stage III-IV) usually have a much poorer prognosis, with the five-year survival rate falling to less than 20%.10 Immunotherapy combined with chemotherapy is emerging as a new standard of care for advanced endometrial cancer, particularly for patients with dMMR disease, who make up approximately 20-30% of all patients.11-14 There is a significant need for new treatment options, especially for the 70-80% of patients with pMMR disease.15,16

In Europe, nearly 125,000 women were diagnosed with endometrial cancer in 2022.17,18

DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi (durvalumab) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy versus platinum-based chemotherapy alone as a treatment for patients with newly diagnosed advanced or recurrent endometrial cancer.

The DUO-E trial randomised 699 patients with newly diagnosed advanced or recurrent epithelial endometrial carcinoma to receive either Imfinzi (1120mg) or placebo, given every three weeks in addition to standard-of-care platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg) or placebo every four weeks as maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day]) or placebo until disease progression.

The dual primary endpoint was progression-free survival (PFS) of each treatment arm versus standard-of-care chemotherapy alone, and both arms demonstrated a statistically significant and clinically meaningful improvement in PFS compared to standard of care in patients with newly diagnosed advanced or recurrent endometrial cancer.1 Key secondary endpoints included overall survival (OS), safety and tolerability. The trial continues to assess OS for both arms in the overall trial population. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.

For more information about the trial, please visit ClinicalTrials.gov.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy. Imfinzi is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC.

Imfinzi also demonstrated statistically significant and clinically meaningful event-free survival results in patients with resectable early-stage NSCLC based on the AEGEAN Phase III trial. Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery is approved for patients in Switzerland and the UK based on this trial.

In limited-stage SCLC, Imfinzi demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of OS and PFS compared to placebo in patients who had not progressed following standard-of-care concurrent chemoradiotherapy in the ADRIATIC Phase III trial.

In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in combination with chemotherapy (carboplatin and paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient in the US.

Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, breast cancer, bladder cancer, several gastrointestinal and gynaecologic cancers and other solid tumours.

Lynparza
Lynparza is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination-related (HRR) genes, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents [NHAs]).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza may also help enhance immunogenicity and increase the impact of anti-tumour immune responses.

Lynparza is currently approved in a number of countries across multiple tumour types, including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for germline BRCA mutation (gBRCAm), HER2-negative metastatic breast cancer (in the EU and Japan, this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan, this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated (EU only) and for BRCAm mCRPC (US and Japan); and as monotherapy for HRR gene-mutated mCRPC in patients who have progressed on prior NHA treatment (BRCAm only in the EU and Japan). In China, Lynparza is approved for the treatment of BRCA-mutated mCRPC as well as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer.

Lynparza is being jointly developed and commercialised by AstraZeneca and MSD, both as a monotherapy and in combination with other potential medicines. Independently, the companies are developing and will commercialise Lynparza in combination with their respective PD-L1 and PD-1 medicines, Imfinzi (durvalumab) and Keytruda (pembrolizumab). Lynparza has been used to treat approximately 140,000 patients worldwide. Lynparza has a broad clinical trial development programme, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.