On August 6, 2024 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported second quarter 2024 financial results and provided updates across the company’s hematology and genetic disease franchises (Press release, Beam Therapeutics, AUG 6, 2024, View Source [SID1234645407]).

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"This quarter we’ve made significant progress across our rapidly expanding clinical portfolio, where each program utilizes the power and precision of base editing technology to provide potential best-in-class genetic medicines for patients," said John Evans, chief executive officer of Beam. "In our genetic disease franchise, we’re pleased to announce the clearance of our U.S. investigational new drug (IND) application for BEAM-301, our first U.S. in vivoregulatory filing. We’re focused on initiating site activation activities for BEAM-301 as well as continuing to enroll our BEAM-302 Phase 1/2 clinical trial in alpha-1 antitrypsin deficiency (AATD) following study initiation in June. We look forward to reporting the first data from the BEAM-302 trial next year. In addition, enrollment in the BEACON trial of BEAM-101 in sickle cell disease (SCD) has exceeded expectations, with more than 20 patients enrolled and six dosed, plus additional patients consented and in the screening process. Initial BEAM-101 clinical data have been submitted for presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place in December, along with abstracts for the first clinical data for BEAM-201 as well as our first ESCAPE preclinical data in non-human primates."

Second Quarter 2024 and Recent Progress

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To date, more than 20 patients have cleared screening and enrolled in the BEACON Phase 1/2 clinical trial of BEAM-101, an investigational genetically modified cell therapy for the treatment of SCD. Of these patients, six have been dosed with BEAM-101, with the other enrolled patients going through pre-transplant stages including mobilization and manufacturing.
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In June, Beam reported data at the European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress highlighting its optimized, closed and automated manufacturing process for its base-edited CD34+ hematopoietic stem and progenitor cell genetic medicines, which is currently being deployed for the manufacturing of BEAM-101 in the BEACON Phase 1/2 clinical trial. The data, which include both preclinical and GMP clinical manufacturing experience to date, demonstrate that the use of base editing technology plus the advanced CD34+ manufacturing process employed by Beam are achieving reproducible and robust product yields and viability that meet high-quality standards.
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In June, Beam announced that the first patient was treated with BEAM-302, an investigational in vivo base editing medicine designed to precisely correct the underlying cause of severe AATD that is currently being evaluated in a Phase 1/2 clinical trial.
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The U.S. Food and Drug Administration has cleared the IND application for BEAM-301, an investigational in vivo base editing medicine designed to directly correct the R83C mutation, one of the primary disease-causing mutations of glycogen storage disease type Ia (GSDIa).
Key Anticipated Milestones

Hematology Franchise

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Initial data from the BEACON Phase 1/2 clinical trial have been submitted for presentation at the ASH (Free ASH Whitepaper) Annual Meeting, taking place December 7-10, 2024. Pending acceptance, Beam anticipates presenting data on all patients from the sentinel cohort as well as multiple patients from the expansion cohort.
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Beam continues to advance and invest in its Engineered Stem Cell Antibody Paired Evasion (ESCAPE) conditioning platform and anticipates initiating Phase 1-enabling preclinical studies for the program in 2024. Preclinical data for ESCAPE in non-human primates have been submitted for presentation at ASH (Free ASH Whitepaper).
Genetic Disease Franchise

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Beam continues to enroll the Phase 1/2 clinical trial of BEAM-302 in patients with AATD and expects to report initial clinical data in 2025.
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The company is now initiating site activation activities for the Phase 1/2 clinical trial for BEAM-301 in GSDIa with patient dosing expected to commence in early 2025.
Oncology

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Initial data from the Phase 1/2 clinical trial of BEAM-201, a multiplex-edited allogeneic CAR-T product candidate for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL), have been submitted for presentation at the ASH (Free ASH Whitepaper) Annual Meeting.
Second Quarter 2024 Financial Results

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Cash Position: Cash, cash equivalents and marketable securities, were $1.0 billion as of June 30, 2024, compared to $1.2 billion as of December 31, 2023.
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Research & Development (R&D) Expenses: R&D expenses were $87.0 million for the second quarter of 2024, compared to $97.6 million for the second quarter of 2023.
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General & Administrative (G&A) Expenses: G&A expenses were $29.6 million for the first quarter of 2024, compared to $24.7 million for the second quarter of 2023.
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Net Loss: Net loss was $91.1 million for the second quarter of 2024, or $1.11 per share, compared to $82.8 million for the second quarter of 2023, or $1.08 per share.
Cash Runway

Beam expects that its cash, cash equivalents and marketable securities as of June 30, 2024, will enable the company to fund its anticipated operating expenses and capital expenditure requirements into 2027. This expectation includes funding directed toward reaching each of the key anticipated milestones for BEAM-101, ESCAPE, BEAM-301 and BEAM-302 described above, as well as continued investments in platform advancements and manufacturing capabilities, and excludes commercial spend related to the potential launch of BEAM-101.

On August 6, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the quarter ended June 30, 2024, and highlighted select corporate milestones and progress on its key clinical development programs (Press release, Karyopharm, AUG 6, 2024, View Source [SID1234645423]).

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"We are pleased with the strength of our commercial performance with consecutive quarter-over-quarter growth in the highly competitive multiple myeloma marketplace and look forward to leveraging the foundation that we have built in this indication to serve additional patients. Looking ahead with our improved capital structure following our debt refinancing and disciplined expense management, we are strongly positioned for our next stage of growth, to redefine the standard of care for patients with myelofibrosis and endometrial cancer, driven by selinexor’s growing body of compelling clinical and preclinical data in these indications," said Richard Paulson, President and Chief Executive Officer of Karyopharm.

Second Quarter 2024 and Recent Highlights

XPOVIO Commercial Performance

Achieved U.S. net product revenue of $28.0 million for the second quarter of 2024, compared to $26.0 million for the first quarter of 2024 and $28.5 million for the second quarter of 2023.

XPOVIO net product revenue was supported by quarter-over-quarter growth in both new patient starts and refills.

Continued quarter-over-quarter growth with > 10% growth in the community setting, which represents ~60% of overall net product revenues. In the academic setting, demand for XPOVIO was consistent quarter-over-quarter amidst ongoing competitive pressures, driven by the expanding use of XPOVIO immediately preceding and following T-cell therapies in later lines. The vast majority of XPOVIO new patient mix continues to be in the second to fourth lines of therapy.

Continued global momentum in the second quarter of 2024 with favorable reimbursement decisions in the United Kingdom and South Korea, and additional regulatory approvals in relapsed/refractory (R/R) DLBCL in mainland China and R/R multiple myeloma in multiple international markets.
Research and Development (R&D) Highlights

Myelofibrosis

Pre-clinical data were presented on the mechanism of action for XPO1 inhibition in myelofibrosis targeting multiple oncogenic pathways beyond JAK/STAT, including inhibition of NF-κB-driven proinflammatory cytokines and p53-mediated cell cycle regulation, at the June 2024 European Hematology Association (EHA) (Free EHA Whitepaper) meeting. These data suggest that XPO1 may be fundamental in myelofibrosis, providing the mechanistic rationale for both monotherapy as well as additive, if not synergistic, activity in combination with ruxolitinib, which we believe further supports the promising clinical results, including durable spleen volume reduction and symptom improvement, observed to date from the Phase 1 trial.

Pivotal SENTRY Phase 3 trial of selinexor in combination with ruxolitinib in JAK-naive myelofibrosis continues to enroll with strong momentum, supported by high interest from investigators and minimal competition from other therapies in the JAK-naïve setting; expected top-line data readout on track for 2H 2025.
Endometrial Cancer

Long-term follow-up data from a pre-specified exploratory subgroup analysis of patients with advanced or recurrent TP53 wild-type endometrial cancer from the SIENDO study (NCT03555422) were presented at "ASCO Plenary Series: Rapid Abstract Updates" oral session at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2024.

In the exploratory subgroup analysis from the Phase 3 SIENDO Study, 113 patients with TP53 wild-type advanced/recurrent endometrial cancer were randomized to receive selinexor (n=77) vs placebo (n=36) as maintenance therapy after 1L platinum-based chemotherapy. As of the April 1, 2024 data cut-off date, and a median duration of follow-up of 36.8 months, selinexor-treated patients had a median PFS of 28.4 months compared to 5.2 months for patients receiving placebo. In selinexor-treated patients with TP53 wild-type/pMMR and TP53 wild-type/dMMR endometrial cancer, the median PFS was 39.5 months and 13.1 months compared to 4.9 months and 3.7 months in those treated with placebo, respectively. Although immature, overall survival (OS) in the TP53 wild-type subgroup was promising, with a hazard ratio of 0.65; median OS for selinexor has not been reached as of the data cut-off date. No new safety signals were identified as of the data cut-off date of April 1, 2024. The most common treatment-emergent adverse events in selinexor treated TP53 wild-type patients were nausea (90%), vomiting (60%) and diarrhea (45%), the majority of which were grades 1-2.

The updated SIENDO analysis also highlighted findings from an exploratory quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) used to assess quality and toxicity-adjusted PFS. The findings showed the restricted mean Q-TWiST for selinexor to be 26 months compared to 15 months for placebo, resulting in a difference of nearly 11 months.

Pivotal XPORT-EC-042 Phase 3 trial in TP53 wild-type endometrial cancer is now expected to read-out top-line data in early 2026, primarily due to higher-than-expected screen failure rates.
Multiple Myeloma

Updated clinical data on SPd (selinexor in combination with pomalidomide and dexamethasone) regimen from STOMP and MM-028 trials were published in the Frontiers of Oncology Journal in May 2024. Both the Phase 1b/2 Selinexor and Backbone Treatments of Myeloma Patients (STOMP) trial (NCT02343042) and the Phase 2b XPORT-MM-028 (NCT04414475) trials are evaluating multiple selinexor combinations, including SPd, in patients with relapsed or refractory multiple myeloma (RRMM). The updated results for SPd 40 mg from these studies showed a median PFS of 18.4 months and a manageable safety profile with no new safety signals.

Pivotal XPORT-MM-031 (EMN29) Phase 3 trial, an oral combination of selinexor 40 mg, pomalidomide and dexamethasone in patients with previously treated multiple myeloma, is enrolling patients at a lower rate than expected in an increasingly global competitive clinical trial environment targeting a similar patient population. Given this evolving environment and the positive SPd 40 mg PFS data published from the STOMP and MM-028 trials, Karyopharm intends to work with the trial’s sponsor, the European Myeloma Network, to amend certain aspects of the design for this trial, including a reduction in the number of patients that are targeted for enrollment, and the statistical plan. With these updates, Karyopharm expects top-line data readout in 1H 2025; there remains a potential to seek regulatory approval pending the outcome of the study results.
KPT-9274 (Padnarsertib)

KPT-9274, a first-in-class, oral small molecule and a dual inhibitor of PAK4 and NAMPT that was discovered at Karyopharm, was granted two Rare Pediatric Disease Designations (RPDD) by the U.S. Food and Drug Administration (FDA) for the treatment of Rhabdomyosarcoma (RMS) and for the treatment of Ewing sarcoma (EWS) in June 2024. The FDA further granted KPT-9274 two Orphan Drug Designations in July 2024 for the treatment of soft tissue sarcoma, which includes RMS, and for the treatment of EWS. RMS and EWS are rare cancers of the bone or soft tissue, primarily diagnosed in pediatric patients, with poor survival outcomes and high unmet need for new therapies. KPT-9274 showed tumor regressions and decreased metastatic properties in pediatric RMS and EWS pre-clinical models. Karyopharm is evaluating out-licensing and/or partnership opportunities for further advancement of this program.
Financing Transactions and 2024 Financial Outlook

In May 2024, the Company completed certain financing transactions which extended the vast majority of its debt maturities into 2028 and 2029 and amended its royalty agreement with HealthCare Royalty, further strengthening its balance sheet.
Based on its current operating plans, Karyopharm has updated its guidance for full year 2024 as follows:

Total revenue to be in the range of $145.0 million to $160.0 million as compared to initial guidance of $140.0 million to $160.0 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners.

U.S. XPOVIO net product revenue to be in the range of $105.0 million to $120.0 million as compared to initial guidance of $100.0 million to $120.0 million.

R&D and selling, general and administrative (SG&A) expenses to be in the range of $250.0 million to $265.0 million, which includes approximately $20.0 million estimated non-cash stock-based compensation expense, as compared to initial guidance of $260.0 million to $280.0 million including $20.0 million to $25.0 million of estimated non-cash stock-based compensation expense.

The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO net product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into the first quarter of 20261 aided by ongoing disciplined expense management and initiated cost saving measures.
1 Excluding re-payment of $24.5 million aggregate principal amount of the Company’s remaining senior convertible notes due 2025 and $25.0 million minimum liquidity covenant under the senior secured term loan due 2028.

Second Quarter 2024 Financial Results

Total revenue: Total revenue for the second quarter of 2024 was $42.8 million, compared to $37.6 million for the second quarter of 2023.

Net product revenue: Net product revenue for the second quarter of 2024 was $28.0 million, compared to $28.5 million for the second quarter of 2023.

License and other revenue: License and other revenue for the second quarter of 2024 was $14.8 million, compared to $9.1 million for the second quarter of 2023. The increase was primarily due to $4.0 million of milestone-related revenue recognized from Menarini in 2024 and a $2.3 million increase in revenue for the reimbursement of development-related expenses from Menarini due to an increase in the corresponding expenses.

Cost of sales: Cost of sales for the second quarter of 2024 was $1.5 million, compared to $1.2 million for the second quarter of 2023. Cost of sales reflects the costs of XPOVIO units sold and the costs of products sold to our partners.

R&D expenses: R&D expenses for the second quarter of 2024 were $38.4 million, compared to $31.5 million for the second quarter of 2023. The increase was primarily due to an increase in clinical trial and related costs, related mainly to increased activity in our ongoing pivotal Phase 3 trials in myelofibrosis and multiple myeloma, including increased purchases of comparator drugs.

SG&A expenses: SG&A expenses for the second quarter of 2024 were $31.1 million, compared to $34.5 million for the second quarter of 2023. The decrease was primarily due to our ongoing cost reduction initiatives and lower headcount.

Interest income: Interest income for the second quarter of 2024 was $1.9 million, compared to $2.8 million for the second quarter of 2023.

Interest expense: Interest expense for the second quarter of 2024 was $8.9 million, compared to $5.8 million for the second quarter of 2023. The increase in interest expense was due to the Company’s new term loan and new secured convertible senior notes.

Gain on extinguishment of debt and other income: The Company recognized a non-cash gain on extinguishment of debt of $44.7 million and other income of $14.3 million during the second quarter of 2024, which related to the refinancing transactions that were completed during the second quarter of 2024.

Net income (loss): Karyopharm reported net income of $23.8 million, or $0.15 income per basic share and $0.20 loss per diluted share, for the second quarter of 2024, compared to a net loss of $32.6 million, or $0.29 loss per basic and diluted share, for the second quarter of 2023.

Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2024 totaled $152.5 million, compared to $192.4 million as of December 31, 2023.

Conference Call Information

Karyopharm will host a conference call today, August 6, 2024, at 8:00 a.m. Eastern Time, to discuss the second quarter 2024 financial results and provide business highlights. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website. An archived webcast will be available on the Company’s website approximately two hours after the event.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).

For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

On August 6, 2024 Daiichi Sankyo (TSE: 4568) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported to have expanded their existing global co-development and co-commercialization agreement for three investigational DXd antibody-drug conjugates to include Merck’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager (Press release, Merck & Co, AUG 6, 2024, https://www.merck.com/news/daiichi-sankyo-and-merck-enter-into-global-development-and-commercialization-agreement-for-mk-6070/ [SID1234645440]). The companies will jointly develop and commercialize MK-6070 worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for MK-6070.

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MK-6070 is a T-cell engager targeting DLL3, an inhibitory canonical Notch ligand that is expressed at high levels in small cell lung cancer (SCLC) and neuroendocrine tumors, currently being evaluated in a Phase 1/2 clinical trial (NCT04471727). The companies are planning to evaluate MK-6070 in combination with ifinatamab deruxtecan (I-DXd) in certain patients with SCLC, as well as other potential combinations. Merck obtained MK-6070 through its acquisition of Harpoon Therapeutics.

"Expanding our oncology pipeline with a DLL3 T-cell engager further supports Daiichi Sankyo’s strategy to create new standards of care for patients with cancer worldwide," said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo. "We look forward to continuing our relationship with Merck with the addition of MK-6070 as it provides potential synergies with our established antibody-drug conjugate collaboration, particularly ifinatamab deruxtecan, and demonstrates our shared commitment to advancing new medicines for patients."

"Small cell lung cancer is an aggressive, fast-growing form of lung cancer and new treatment approaches are urgently needed," said Dr. Dean Y. Li, president, Merck Research Laboratories. "We are pleased to build upon our collaboration with Daiichi Sankyo and look forward to evaluating the novel combination of MK-6070 and ifinatamab deruxtecan in small cell lung cancer and other forms of cancer."

Financial highlights

Under the terms of the agreement, Merck will receive an upfront cash payment of $170 million and has also satisfied a contingent quid obligation from the original collaboration agreement. The companies will share R&D and commercialization expenses as well as profits worldwide, except for Japan where Merck retains exclusive rights and Daiichi Sankyo receives a royalty based on sales. R&D expenses related to MK-6070 in combination with ifinatamab deruxtecan will be shared in a manner consistent with the original agreement for ifinatamab deruxtecan. Merck will generally record sales for MK-6070 worldwide.

About DLL3

Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is highly expressed on SCLC and other neuroendocrine tumors such as melanoma, small cell bladder cancer and metastatic castration resistant prostate cancer and is minimally expressed in normal tissues. DLL3 is a promising therapeutic target where multiple treatment approaches are being explored.

About MK-6070

MK-6070 is an investigational DLL3 directed tri-specific T-cell engager currently being evaluated in a Phase 1/2 clinical trial as a monotherapy in certain patients with advanced cancers associated with expression of DLL3 and in combination with atezolizumab in certain patients with SCLC. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to MK-6070 for the treatment of SCLC in March 2022.

About the Daiichi Sankyo and Merck collaboration

Daiichi Sankyo and Merck (known as MSD outside of the United States and Canada) entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.

On August 6, 2024 SEED Therapeutics Inc. ("SEED"), a biotechnology company focused on harnessing and engineering Molecular Glues for targeted protein degradation (TPD) of disease-causing proteins, reported a strategic research collaboration with Eisai Co., Ltd. ("Eisai") to discover, develop, and commercialize novel molecular glue degraders for multiple undisclosed neurodegeneration and oncology targets (Press release, Seed Therapeutics, AUG 6, 2024, View Source [SID1234645408]). The collaboration is coupled with a Series A-3 financing led by Eisai.

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Key Aspects of the SEED – Eisai Collaboration:

Collaboration Roles: SEED will lead preclinical discovery activities for the selected targets, including E3 ligase selection and identification of the appropriate molecular glue degraders. Eisai will have exclusive rights to develop and commercialize compounds derived from this collaboration.
Financial Terms: SEED is entitled to receive upfront payment and preclinical, clinical, regulatory and sales milestone payments of up to $1.5 billion, plus tiered royalties upon Eisai’s exercise of their exclusive rights under the strategic research collaboration.
The SEED–Eisai collaboration follows a separate and on-going research collaboration between SEED and Eli Lilly to discover and develop Molecular Glue Degraders for undisclosed targets. (Click here for related press release.)

Series A-3 Financing:

SEED also announces a Series A-3 financing with a first close of $24 million from investors led by Eisai. A second close is targeted for Q4 2024.

The Series A-3 financing is expected to further accelerate SEED’s clinical development of internal proprietary programs in cancer and in neurodegeneration, expand its TPD platform and pipeline, and supplement prior investments from Eli Lilly and BeyondSpring.

SEED will advance its internal, potentially "best-in-class" oral RBM39 Degrader into Phase 1 safety/efficacy testing beginning in 2025 for rationally selected, biomarker-driven cancer indications. SEED’s program will build on Eisai’s pioneering discovery of a class of RBM39 degraders over three decades.
SEED will also progress its internal Tau degrader program (for Alzheimer’s disease) into in vivo efficacy in 2025, and IND in 2026.
SEED will scale its proprietary TPD platform development. With global neurodegeneration drug development leaders Eisai and Eli Lilly as investors and research collaborators, SEED will extend its research and thought leadership in the discovery and development of oral Molecular Glues for the treatment of neurodegenerative diseases.

Dr. Takashi Owa, Eisai’s Chief Scientific Officer stated: "SEED has a cutting-edge technology platform to discover a class of molecular-glue target protein degraders, one of the most highlighted modalities in the modern drug discovery. While the anti-myeloma drug lenalidomide from the molecular-glue class has been successful in the oncology field, our research collaboration will also focus on utilizing this modality in the neurology field. Our collaboration with SEED is unique and clearly differentiated, and I look forward to learning of the important progress being made by both companies to achieve Social Good."

Dr. Lan Huang, SEED’s Co-Founder, Chairman, and CEO added, "We are honored to collaborate with Eisai, a world-leading drug development powerhouse, to discover impactful medicines for undruggable targets. Looking ahead, SEED’s unique Molecular Glue discovery platform on neurodegenerative disease will be further strengthened through our collaborations with both Eli Lilly and Eisai (under separate collaboration agreements), two global pioneers in the timely development of treatments for neurodegeneration, including approved therapies for Alzheimer’s disease. Finally, having demonstrated the scalability and versatility of our TPD platform through the success of multiple pipeline programs across various key therapeutic indications, our Series A-3 financing and non-dilutive funding of R&D milestone payments from both Eli Lilly and Eisai, SEED is well-positioned to advance our internal high-profile programs into clinics, and to create great value for patients and our shareholders."

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On August 6, 2024 Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) today reported financial results for the three and six months ended June 30, 2024, and provided an operating forecast and business update (Press release, Ligand, AUG 6, 2024, View Source [SID1234645424]). Ligand management will host a conference call and webcast today at 4:30 p.m. Eastern Time to discuss this announcement and answer questions.

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"We had a strong quarter and are on track to meet the long-term growth objectives we outlined in December," said Todd Davis, CEO of Ligand. "We added four new commercial-stage programs in the first half of this year, including QARZIBA, an orphan oncology product we acquired following the APEIRON Biologics transaction, Merck’s CAPVAXIVE and Verona Pharma’s Ohtuvayre, which received FDA approval in the second quarter, and Pelthos’ ZELSUVMI which was approved by the FDA earlier this year. Also, our partner, Primrose Bio secured additional outside capital which will enable them to continue building their business, fortifying the value of our long-term interest in the company. These developments underscore our commitment to expand our royalty portfolio, which now includes 12 major commercial-stage programs, double the number of programs we had at the beginning of 2023."

Second Quarter 2024 Financial Results
Total revenues and other income for the second quarter of 2024 were $41.5 million, compared with $26.4 million for the same period in 2023 with the increase primarily due to an increase in royalty revenue and milestone payments earned upon the approval of several key programs. Royalties for the second quarter of 2024 were $23.2 million, compared with $20.9 million for the same period in 2023, with the increase primarily attributable to an increase in sales of Travere Therapeutics’ (Nasdaq:TVTX) FILSPARI and Amgen’s (Nasdaq:AMGN) KYPROLIS. Captisol sales were $7.5 million for the second quarter of 2024, compared with $5.2 million for the same period in 2023, with the change due to the timing of customer orders. Contract revenue and other income was $10.9 million for the second quarter of 2024, compared with $0.2 million for the same period in 2023, with the increase driven by the $5.8 million milestone payment earned upon FDA approval of Ohtuvayre, the $2.0 million milestone payment earned upon FDA approval of CAPVAXIVE, and the $2.3 million milestone payment earned upon the conditional marketing approval of FILSPARI by the European Commission.
Cost of Captisol was $2.9 million for the second quarter of 2024, compared with $1.7 million for the same period in 2023, with the increase due to higher Captisol sales. Amortization of intangibles was $8.3 million for the second quarter of 2024, compared with $8.5 million for the same period in 2023. Research and development expense was $5.4 million for the second quarter of 2024, compared with $6.9 million for the same period in 2023, with the decrease primarily attributed to lower employee related expenses and lab supplies resulting from the Pelican spin-off in September 2023. The decrease was partially offset by the additional operating costs associated with incubating the Pelthos business. General and administrative expense was $17.6 million for the second quarter of 2024, compared with $11.3 million for the same period in 2023, with the increase primarily attributed to higher stock-based compensation and operating costs associated with incubating the Pelthos business.
GAAP net loss from continuing operations for the second quarter of 2024 was $51.9 million, or $2.88 per share, compared with GAAP net income from continuing operations of $2.3 million, or $0.13 per diluted share, for the same period in 2023. GAAP net loss from continuing operations for the second quarter of 2024 included a $13.8 million non-cash unrealized loss from short-term investments associated with Viking Therapeutics (Nasdaq: VKTX) stock, a $26.5 million decrease in the carrying value of our investments, primarily in connection with Takeda

Pharmaceutical’s (NYSE:TAK) soticlestat, and a $33.8 million decrease in our investments in Primrose Bio (private). Our equity ownership interest in Primrose Bio has decreased from 49.9% to 34.3% in connection with their recent financing round. The financing round was at a valuation below the value arrived at when we spun out the Pelican business in September 2023, which resulted in a non-cash reduction in the carrying value of our investment. Adjusted net income from continuing operations for the second quarter of 2024 was $25.8 million, or $1.40 per diluted share, compared to $25.1 million, or $1.42 per diluted share, for the same period in 2023. Excluding the impact of gains from sales of Viking Therapeutics stock in the second quarter of 2023, core adjusted net income from continuing operations for the second quarter of 2023 was $11.7 million, or $0.66 per diluted share. We did not sell any shares of Viking Therapeutics stock in the second quarter of 2024. The increase in core adjusted net income is driven primarily by the 58% increase in revenue. See the table below for a reconciliation of net income from continuing operations to adjusted net income from continuing operations.
As of June 30, 2024, Ligand had cash, cash equivalents and short-term investments of $226.9 million which includes $53.0 million in Viking Therapeutics common stock. In May 2024, Ligand entered into a collar option agreement to hedge against Viking Therapeutics stock price fluctuation risk. Ligand recorded a $15.2 million unrealized gain associated with the collar option agreement during the second quarter of 2024 and the value of that derivative asset is classified as other current assets. On July 8, 2024, Ligand entered into an amended credit agreement with Citibank, N.A., which expands the existing $75 million revolving credit facility to $125 million with a maturity date of October 12, 2026.

Year-to-Date Financial Results
Total revenues and other income for the six months ended June 30, 2024 were $72.5 million, compared with $70.3 million for the same period in 2023. Royalties for the six months ended June 30, 2024 were $42.3 million, compared with $38.6 million for the same period in 2023, with the increase primarily attributable to Amgen’s KYPROLIS, Jazz Pharmaceuticals’ RYLAZE, Merck and Co.’s (NYSE: MRK) VAXNEUVANCE and Travere Therapeutics’ FILSPARI, partially offset by a decline in royalties in CASI Pharmaceuticals Inc.’s (Nasdaq: CASI) EVOMELA and Alvogen’s teriparatide. Captisol sales were $16.7 million for the six months ended June 30, 2024, compared with $15.8 million for the same period in 2023, with the change due to the timing of customer orders. Contract revenue and other income was $13.5 million for the six months ended June 30, 2024, compared with $15.9 million for the same period in 2023, with the decrease driven by a $15.3 million milestone payment earned from Travere Therapeutics upon the FDA approval of FILSPARI in the prior year period, partially offset by the above mentioned current year milestone payments earned.
Cost of Captisol was $5.8 million for the six months ended June 30, 2024, compared with $5.4 million for the same period in 2023, with the increase due to higher total Captisol sales. Amortization of intangibles was $16.4 million for the six months ended June 30, 2024, compared with $17.1 million for the same period in 2023. Research and development expense was $11.3 million for the six months ended June 30, 2024, compared with $13.5 million for the same period in 2023, with the decrease primarily attributed to lower employee related expenses and lab supplies resulting from the Pelican spin-off in September 2023. The decrease was partially offset by additional costs associated with incubating the Pelthos business. General and administrative expense was $28.6 million for the six months ended June 30, 2024, compared with $22.1 million for the same period in 2023, with the increase driven by higher stock-based compensation expense and additional costs associated with incubating the Pelthos business.
GAAP net income from continuing operations for the six months ended June 30, 2024 was $34.2 million, or $1.87 per diluted share, compared with GAAP net income from continuing operations of $45.9 million, or $2.57 per diluted share, for the same period in 2023. The decrease in GAAP net income from continuing operations from the prior year period is due primarily to a $26.5 million decrease mainly in the fair value of our investment in Takeda’s soticlestat and a $36.1 million decrease in our investments in Primrose Bio during the six months ended June 30, 2024, partially offset by the realized gains from short-term investments associated with Viking Therapeutics stock of $60.0 million. Adjusted net income from continuing operations for the six months ended June 30, 2024 was $95.5 million, or $5.23 per diluted share, compared to $65.0 million, or $3.69 per diluted share, for the same period in 2023. Excluding the impact of gains from sales of Viking Therapeutics stock, core adjusted net income from continuing operations for the six months ended June 30, 2024 was $47.6 million, or $2.61 per diluted share, compared with $35.1 million, or $1.99 per diluted share, for the same period in 2023. The increase in core adjusted net income is primarily driven by the increase in adjusted operating income. See the table below for a reconciliation of net income from continuing operations to adjusted net income from continuing operations.

2024 Financial Guidance
Ligand is reaffirming its 2024 financial guidance given on July 8, 2024. The Company expects 2024 royalties to range from $100 million to $105 million, sales of Captisol to range from $25 million to $27 million, and contract revenue to range from $15 million to $25 million. These revenue components result in total revenue forecast of $140 million to $157 million. Core adjusted earnings per diluted share are expected to range from approximately $5.00 to $5.50. This guidance excludes the $60 million realized gain from short-term investments on the sale of Viking Therapeutics stock.

Adjusted Financial Measures
Ligand reports adjusted net income and adjusted net income per diluted share in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The Company’s financial measures under GAAP include share-based compensation expense, amortization of debt-related costs, amortization related to acquisitions and intangible assets, amortization of financial royalty assets, changes in contingent liabilities, mark-to-market adjustments for amounts relating to its equity investments in public companies, excess tax benefit from share-based compensation, Pelthos operating loss, impairment of financial royalty assets, loss from equity method investment in Primrose Bio, income tax effect of adjusted reconciling items and others that are listed in the itemized reconciliations between GAAP and adjusted financial measures included at the end of this press release. However, the Company does not provide reconciliations of such forward-looking adjusted measures to GAAP due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation, including non-cash adjustments that could be made for changes in contingent liabilities, changes in the market value of its investments in public companies, share-based compensation expense and the effects of any discrete income tax items. Management has excluded the effects of these items in its adjusted measures to assist investors in analyzing and assessing the Company’s past and future core operating performance. Additionally, adjusted earnings per diluted share is a key component of the financial metrics utilized by the Company’s board of directors to measure, in part, management’s performance and determine significant elements of management’s compensation.

Second Quarter 2024 and Recent Updates
Business Highlights
On July 8, Ligand announced the $100 million acquisition of APEIRON Biologics, a private biotech company based in Vienna, Austria. Apeiron holds the royalty rights to QARZIBA (dinutuximab beta) for the treatment of high-risk neuroblastoma. QARZIBA was approved by the European Medicines Agency in 2017 and is commercially available today in more than 35 countries. QARZIBA is marketed outside of mainland China by the global pharmaceutical company Recordati S.p.A., which acquired EUSA Pharma (UK) Limited in 2022.
On July 8, Ligand also amended its revolving credit facility with Citibank. The Credit Agreement was amended to, among other things, increase the aggregate revolving credit facility amount from $75 million to $125 million.
On July 24, Palvella Therapeutics, Inc. (private) announced a merger agreement with Pieris Pharmaceuticals, Inc. (Nasdaq: PIRS) in which Palvella anticipates becoming a publicly traded rare disease company upon the close of the merger. In connection with the proposed merger, Palvella secured commitments from a syndicate of leading specialist biotech investors in an oversubscribed $78.9 million concurrent private financing.
The transaction will help advance several clinical milestones for Palvella:
•A Phase 3 pivotal study of QTORIN 3.9% rapamycin anhydrous gel for the treatment of microcystic lymphatic malformations, a serious, rare genetic and lifelong disease for which there are no FDA-approved therapies. The disease impacts more than 30,000 diagnosed patients in the U.S. QTORIN rapamycin has been granted FDA’s Breakthrough Therapy, Fast Track, and Orphan Designations for the treatment of microcystic lymphatic malformations.
•A Phase 2 study of QTORIN rapamycin for the treatment of cutaneous venous malformations. Cutaneous venous malformations are a serious, rare genetic disease which can cause functional impairment, significantly impact quality of life, and are associated with severe long-term complications. QTORIN rapamycin has been granted FDA’s Fast Track Designation for the treatment of venous malformations.

Notably, if approved, QTORIN rapamycin has the potential to be the first approved therapy and standard of care in the U.S. for microcystic lymphatic malformations and cutaneous venous malformations.
As background, Palvella was originally sourced through Ligand’s proactive deal origination efforts. Since Ligand’s first transaction with Palvella, the company has secured significant subsequent equity funding from leading biotech investors, including BVF Partners, Petrichor, Samsara BioCapital, and others. Ligand is entitled to a royalty of 8-9.8% on worldwide commercial sales of QTORIN rapamycin. In addition to Ligand’s royalty, Ligand anticipates owning approximately 2% of the combined company following the close of the reverse merger and concurrent financing.
Portfolio Updates
On July 18, Agenus Inc. (Nasdaq: AGEN), announced the results of its end-of-Phase 2 meeting with the FDA, for the advancement of its immunotherapy combination, botensilimab (BOT) and balstilimab (BAL), for the treatment of adult patients with relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC) with no active liver metastases (NLM). Agenus received clarity from the FDA on their Phase III dosing regimen, which is an important achievement. The company also announced topline interim data from its Phase 2 trial, which are showing trends consistent with the Phase 1 study, including an ORR of 19.4% and 6-month survival rate of 90% for the BOT 75mg/BAL combination. The safety profile was manageable and no new signals were observed. Agenus plans to continue future discussions with the FDA as the Phase 2 data mature and will present these data in totality at an upcoming medical conference.

On June 26, Verona Pharma plc (Nasdaq: VRNA) announced FDA approval of Ohtuvayre (ensifentrine), the first inhaled product with a novel mechanism of action available for the maintenance treatment of chronic obstructive pulmonary disease in adult patients in more than 20 years. Ohtuvayre is a first-in-class selective dual inhibitor of the enzymes phosphodiesterase 3 phosphodiesterase 4 ("PDE3 and PDE4") that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule. Ligand earned a $5.8 million milestone payment upon FDA approval of Ohtuvayre and will earn an additional $13.8 million upon its commercial launch which is expected to occur during the third quarter of 2024. Ligand is entitled to a royalty of approximately 3% on future worldwide net sales of Ohtuvayre.

On June 17, Merck announced approval from the FDA for CAPVAXIVE, previously known as V116, a 21 valent pneumococcal vaccine for the prevention of Streptococcus pneumoniae infection. Risk of infection is higher among patients that are immunocompromised, suffering chronic health conditions, and adults aged 50 years or older. As the first pneumococcal conjugate vaccine specifically designed for adults, it covers 21 serotypes that account for approximately 85% of cases of invasive pneumococcal disease among individuals 65 and over, including 8 serotypes not covered by any licensed vaccines. Specific serotypes pose potentially greater risk for invasive pneumococcal disease, including pneumococcal bacteremia and meningitis. Following the FDA approval, Merck announced on June 27, that the U.S. Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices unanimously voted to recommend CAPVAXIVE as an option for all adults age 65 and older, for adults 19 to 64 with certain risk factors, and for those over 65 previously vaccinated with other pneumococcal vaccines. The FDA approval of CAPVAXIVE triggered a $2 million milestone payment to Ligand, and Ligand is entitled to a royalty on future worldwide net sales.

On June 17, Ovid Therapeutics (Nasdaq: OVID) announced Takeda’s SKYLINE study of soticlestat in Dravet syndrome narrowly missed its primary endpoint of reduction in convulsive seizure frequency and showed clinically meaningful and nominal significant effects in multiple key secondary efficacy endpoints. Additionally, Takeda’s SKYWAY study in Lennox-Gastaut syndrome missed its primary endpoint of reduction in major motor drop seizures. Soticlestat had a consistent and favorable safety and tolerability profile in both studies. Takeda indicated that it plans to discuss the totality of the data with regulatory authorities.

On June 17, Marinus Pharmaceuticals (Nasdaq: MRNS) announced topline results from Phase 3 RAISE trial of IV ganaxolone in refractory status epilepticus (RSE). The study met its first co-primary endpoint demonstrating rapid cessation of status epilepticus in a highly refractory patient population but failed to achieve statistical significance on the second co-primary endpoint of the proportion of patients not progressing to IV anesthesia. Marinus said they will continue to analyze the full RAISE dataset and plans to engage with the FDA to discuss a potential path forward for IV ganaxolone in RSE.

On June 4, Viking Therapeutics announced positive, 52-week histologic data from its Phase 2b VOYAGE study of VK2809 in patients with biopsy-confirmed, non-alcoholic steatohepatitis (NASH). The study had successfully achieved its primary endpoint with patients receiving VK2809 experiencing statistically significant declines in liver fat from baseline compared to placebo at 12 weeks. The study also showed an encouraging tolerability and safety profile for VK2809. If development of VK2809 is successful, the program will address a multi-billion dollar market opportunity where Ligand will receive a 3.5% -7.5% royalty on future net sales of VK2809, as well as significant clinical, regulatory, and commercial milestones. Viking plans to schedule an end of Phase 2 meeting with the FDA in the fourth quarter of 2024.

Conference Call and Webcast
Ligand management will host a conference call today beginning at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time) to discuss this announcement and answer questions. To participate via telephone, please dial (800) 715-9871 using the conference ID 8755336. Callers outside the U.S. may dial +1(646) 307-1963. To participate via live or replay webcast, a link is available at View Source