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

On August 6, 2024 Akeso reported the completion of the first patient enrollment in the US for the phase II clinical trial of its innovative CD47 monoclonal antibody, ligufalimab (AK117), in combination with azacitidine for patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) (Press release, Akeso Biopharma, AUG 6, 2024, View Source [SID1234645441]).

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Preliminary studies show that combining AK117 with azacitidine for treating MDS is safe and significantly effective. In response to the urgent need for new therapies among global MDS patients and the evolving market landscape, Akeso has launched an international multicenter Phase II clinical trial. This initiative aims to expedite AK117’s global approval and commercialization process.

CD47-targeted drug development for treating MDS shows promising potential. AK117, a next-generation humanized IgG4 anti-CD47 antibody, effectively blocks the CD47-SIRPα interaction to enhance phagocytic activity against tumor cells by phagocytes.

Recent data presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting demonstrated that AK117 combined with azacitidine significantly reduces anemia and transfusion requirements in MDS patients, with favorable safety and notable efficacy. This positions AK117 as a promising treatment option for MDS patients worldwide.

In the United States alone, approximately 40,000 new cases of MDS are diagnosed annually. High-risk MDS patients typically start with azacitidine as standard therapy, but only 20% to 30% achieve complete remission, underscoring significant unmet clinical needs in global MDS treatment.

In addition to ongoing clinical trials for MDS globally, a Phase II study is underway to evaluate AK117 in combination with venetoclax and AZA as frontline therapy for AML patients who are not eligible for intensive chemotherapy.

Akeso is also actively progressing the global market development of AK117 for solid tumors. Multiple clinical trials exploring AK117’s efficacy with other agents, such as PD-1/VEGF bispecific antibodies and PD-1/CTLA-4 bispecific antibodies, are enrolling participants efficiently.

About Ligufalimab (AK117)
AK117, independently developed by Akeso, is a next-generation humanized lgG4 anti-CD47 antibody without hemagglutination effect. AK117 can bind to CD47 expressed on tumor cells and block the interaction between CD47 and SIRPα, to enhance the phagocytic activity of phagocytes on tumor cells, thereby inhibiting the growth of tumors.

Currently, several phase II clinical trials are underway to investigate the potential of AK117 in combination with azacitidine for hematological tumors, as well as AK117 alone or in combination with ivonescimab and cadonilimab for various solid tumors. Preliminary studies have shown promising efficacy and safety profiles, with no observed dose-limiting toxicity events. Additionally, international multicenter clinical studies evaluating AK117 for treating MDS and AML are enrolling patients.

On August 6, 2024 Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported recent business progress and financial results for the second quarter ended June 30, 2024 (Press release, Bicycle Therapeutics, AUG 6, 2024, View Source [SID1234645409]).

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"In the second quarter, we continued to demonstrate the ongoing progress of our pipeline and highlight the emerging differentiated profiles of our Bicycle Toxin Conjugates zelenectide pevedotin and BT5528 compared to antibody drug conjugates. As we enter the second half of the year, we look forward to sharing the first set of data updates from our clinical programs at the upcoming ESMO (Free ESMO Whitepaper) Congress," said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. "Additionally, I am honored to welcome renowned oncology experts from around the world to our Clinical Advisory Board. Their advice and counsel will be critical as we work to develop therapies that can help patients live longer and live well."

Dr. Lee continued: "Bicycle Therapeutics also significantly strengthened our balance sheet in the second quarter through the support of leading healthcare investors. Moreover, we have prioritized our pipeline and streamlined our leadership team to enable us to focus on the clinical programs and research areas that we believe have the highest potential for value creation and align with our strategy to support the long-term growth of our company."

Second Quarter 2024 and Recent Events

Four abstracts accepted for poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 being held September 13-17 in Barcelona. Bicycle Therapeutics will present four abstracts containing updated clinical data for zelenectide pevedotin (formerly BT8009) in metastatic urothelial cancer (mUC), BT5528 in advanced solid tumors such as mUC and ovarian, and BT7480 in advanced solid tumors.

In June, the company presented two abstracts at the 2024 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting outlining clinical pharmacokinetics of Bicycle Toxin Conjugate (BTC) molecules zelenectide pevedotin and BT5528 compared to antibody drug conjugate enfortumab vedotin and evaluating the emerging safety profile of both BTC molecules, along with an overview of the company’s ongoing Phase 2/3 Duravelo-2 registrational trial of zelenectide pevedotin in mUC.
Focused research and development (R&D) pipeline on clinical programs and research areas that the company believes have the highest potential to maximize value creation. Activities include:
Prioritizing the clinical development of zelenectide pevedotin and BT5528 in multiple tumor types.
Focusing near-term research efforts on advancing the company’s Bicycle Radionuclide Conjugate (BRC) pipeline and the discovery of next-generation BTC molecules.
Except for BT7480, exploring innovative ways to continue development of the company’s immuno-oncology portfolio, including Bicycle Tumor-targeted Immune Cell Agonist (Bicycle TICA) molecules, through collaboration.
Streamlined leadership team to better align with strategic and pipeline priorities.
Michael Skynner, Ph.D., chief technology officer, has assumed leadership of Bicycle Therapeutics’ discovery research team, and all discovery research activities will be consolidated and moved to the company’s headquarters in Cambridge, UK.
Jennifer Perry, Pharm.D., promoted to chief strategy officer and head of commercial. Since joining Bicycle Therapeutics in August 2022, Ms. Perry has been instrumental in establishing and growing Bicycle Therapeutics’ commercial organization. In this expanded role, she will oversee the company’s corporate and end-to-end portfolio strategy while also fulfilling her existing commercial responsibilities. Ms. Perry has more than 20 years of experience in pharma and biotech, with 15 years in oncology. Her experience spans commercial and medical roles with a focus on go-to-market strategies for launching oncology medicines at GSK, Tesaro, TG Therapeutics and Pharmacyclics.
Nick Keen, Ph.D., chief scientific officer, is transitioning to an advisor role with the company as a distinguished fellow, where he will advise the company as needed. The company also hired Eric Westin, M.D., former vice president of clinical development and translational sciences at ImmunoGen, to an advisor role with the company as a distinguished fellow to help refine the company’s translational and clinical strategy.

Formed new Clinical Advisory Board with distinguished global oncology experts to support the advancement of clinical oncology programs. The company expects that the advisors will provide invaluable guidance and insights for the global clinical development of the company’s clinical programs. Inaugural members include:
Charles Swanton, M.D., Ph.D., FRS, FMedSci, FRCP, is the chair of Bicycle Therapeutics’ Clinical Advisory Board and Scientific Advisory Board. He leads the Cancer Evolution and Genome Instability Laboratory at the Francis Crick Institute in London. Dr. Swanton’s research is focused on how tumors evolve over space and time, and he has authored over 250 papers developing an understanding of branching evolutionary histories of solid tumors, processes that drive cancer cell-to-cell variation and the impact of cancer diversity on effective immune surveillance and clinical outcome.
Toni K. Choueiri, M.D., is the director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School. Dr. Choueiri and colleagues have made seminal observations that have defined and evolved the treatment of kidney cancer and led to the approval of several therapies. He has over 800 PubMed-indexed publications and is the lead investigator of multiple national and international Phase 1-3 trials in GU cancers.

Sherene Loi, MBBS (Hons), Ph.D., FRACP, FAHMS, is a medical oncologist specialized in breast cancer treatment and a clinician scientist (lab head) with expertise in genomics, immunology and drug development at the Peter MacCallum Cancer Centre in Melbourne, Australia. She is recognized internationally as a leading clinician scientist whose work has led to new insights into the breast cancer immunology field as well as leading international clinical trials in breast cancer immunotherapy. Professor Loi has published over 330 research articles, co-chairs the International Breast Cancer Study Group and is the Inaugural National Breast Cancer Foundation of Australia Endowed Chair. In 2021, she received the Australian Prime Minister’s Frank Fenner Prize for Life Scientist of the Year.

Solange Peters, M.D., Ph.D., is full professor and chair of medical oncology and the chair of the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Switzerland. She currently oversees teaching and patient care in thoracic malignancies at Lausanne University, and her main fields of interest include new biomarker discovery and validation in preclinical and clinical settings as well as cancer immunotherapy. She is the youngest president of ESMO (Free ESMO Whitepaper), serving for an extended period of 2020-2022. Professor Peters has authored over 500 peer-reviewed manuscripts and book chapters and is associate editor of the Annals of Oncology, deputy editor of Lung Cancer and serves on the editorial board of several other oncology journals. She was the deputy editor of the Journal of Thoracic Oncology for 10 years.

Raised gross proceeds of $555 million in private investment in public equity (PIPE) financing. The PIPE financing, with participation from leading healthcare investors, is expected to extend the company’s financial runway into the second half of 2027. The company plans to use the net proceeds of $544.1 million to fund the continued development of its proprietary pipeline and for other R&D, as well as for general corporate purposes.
Repaid and voluntarily terminated outstanding debt with Hercules. In July 2024, Bicycle Therapeutics announced the repayment of its loan with Hercules Capital, Inc., ahead of its 2025 maturity date, with total payments of $31.9 million, including accrued and unpaid interest, an end-of-term charge and an early repayment fee.
Second Quarter 2024 Financial Results

Cash and cash equivalents were $961.4 million as of June 30, 2024, compared to $526.4 million as of December 31, 2023. The increase in cash and cash equivalents is primarily due to net proceeds from the PIPE financing and share option exercises, offset by cash used in operating activities.
R&D expenses were $40.1 million for the three months ended June 30, 2024, compared to $39.7 million for the three months ended June 30, 2023. The increase in expense of $0.4 million was primarily due to increased clinical program expenses for zelenectide pevedotin development and increased personnel-related expenses, offset by decreased clinical program expenses for Bicycle TICA molecule development, decreased discovery, platform and other expenses and incremental U.K. R&D tax credits.
General and administrative expenses were $15.9 million for the three months ended June 30, 2024, compared to $14.8 million for the three months ended June 30, 2023. The increase of $1.1 million was primarily due to increased personnel-related costs.
Net loss was $39.8 million, or $(0.77) basic and diluted net loss per share, for the three months ended June 30, 2024, compared to net loss of $42.6 million or $(1.41) basic and diluted net loss per share, for three months ended June 30, 2023.

On August 6, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and reported financial results for the quarter ended June 30, 2024 (Press release, MacroGenics, AUG 6, 2024, View Source [SID1234645425]).

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"We are pleased to have the opportunity to present updated safety and efficacy data from our Phase 2 TAMARACK trial of vobra duo at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "In addition, we recently solidified our cash position with the receipt of $100.0 million in milestones, following the positive Phase 3 top-line results from Incyte’s registrational studies of retifanlimab in both anal and lung cancer."

Updates on Proprietary Investigational Programs

Recent progress and anticipated events related to MacroGenics’ investigational product candidates are highlighted below.

B7-H3-Directed Therapies

Vobramitamab duocarmazine (vobra duo) is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation.
The TAMARACK Phase 2 study of vobra duo is being conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks (q4W). MacroGenics completed enrollment of the TAMARACK study in the fourth quarter of 2023, and the study has reached its landmark primary endpoint of 6-month radiographic progression-free survival (rPFS) rate. While mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression and survival.
Updated TAMARACK safety and efficacy data, including the study’s primary endpoint, will be presented in a poster session at the ESMO (Free ESMO Whitepaper) Congress in September 2024. This data will be based on a data cut-off date of July 9, 2024. The abstract submitted to ESMO (Free ESMO Whitepaper) in May was based on an April 12 data cut off. MacroGenics expects to have the mature efficacy findings, including median rPFS, in the second half of 2024 and plans to present the data at a subsequent medical conference.
Following the ESMO (Free ESMO Whitepaper) poster presentation, the Company plans to host a conference call with investors to discuss the TAMARACK data and potential next steps for vobra duo.
MacroGenics continues to enroll a Phase 1/2 dose escalation study of vobra duo in combination with lorigerlimab in patients with various advanced solid tumors. The Company anticipates commencing a dose expansion study of this combination later this year.
MGC026 is a clinical B7-H3-targeting ADC that is site-specifically conjugated to exatecan, a topoisomerase I inhibitor payload developed by Synaffix (a Lonza company). With distinct mechanisms of action, vobra duo and MGC026 may address different cancers, tumor stages, or be used in combination with alternate agents — or potentially with one another — to enhance their clinical utility. A Phase 1 dose escalation study of MGC026 in patients with advanced solid tumors is ongoing.
Lorigerlimab

Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART molecule. In addition to the ongoing study of lorigerlimab in combination with vobra duo mentioned above, MacroGenics is enrolling LORIKEET, a randomized Phase 2 study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current trial design includes a primary study endpoint of rPFS. The Company anticipates completing enrollment of the study in 2024 or early 2025 and providing a clinical update in the first half of 2025.
Emerging ADC Pipeline

MGC028 is a preclinical ADC incorporating an ADAM9-targeting antibody and represents the second MacroGenics ADC molecule that incorporates Synaffix’s novel site-specific linker and topoisomerase I inhibitor-based cytotoxic payload. ADAM9 (a disintegrin and metalloprotease domain 9) is a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment. The Company continues to anticipate submitting an investigational new drug (IND) application for MGC028 by the end of 2024 and initiating a Phase 1 clinical study in 2025.
Partnered Programs

MGD024 is a next-generation, humanized CD123 × CD3 DART molecule designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing. MacroGenics continues to enroll patients in a Phase 1 dose-escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia and myelodysplastic syndromes. Under an October 2022 exclusive option and collaboration agreement, Gilead Sciences, Inc. (Gilead) has the option to license MGD024 at predefined decision points during the Phase 1 study.
ZYNYZ (retifanlimab-dlwr) is a humanized monoclonal antibody targeting PD-1 that the Company licensed to Incyte Corporation (Incyte) in 2017. Incyte recently announced positive Phase 3 top-line results for its registrational studies of retifanlimab in squamous cell carcinoma of the anal canal and non-small cell lung cancer and continues to conduct global studies of retifanlimab across multiple indications.

Subsequent to June 30, 2024, MacroGenics announced the achievement of $100.0 million in milestones from Incyte related to development progress of retifanlimab, following an agreement on July 24, 2024, pursuant to which certain milestones were deemed to have been met. MacroGenics is further eligible to receive up to a total of $210.0 million in remaining development and regulatory milestones and up to $330.0 million in potential commercial milestones from Incyte. MacroGenics receives tiered royalties of 15% to 24% from Incyte on any global net sales of the product and manufactures a portion of Incyte’s global commercial supply of retifanlimab.
Second Quarter 2024 Financial Results

Cash Position: Cash, cash equivalents and marketable securities balance as of June 30, 2024, was $140.4 million, compared to $229.8 million as of December 31, 2023. The June 30, 2024 balance did not include the $100.0 million in milestones subsequently received from Incyte.
Revenue: Total revenue was $10.8 million for the quarter ended June 30, 2024, compared to total revenue of $13.1 million for the quarter ended June 30, 2023. The decrease was primarily due to less revenue recognized under the Provention Asset Purchase Agreement and was partially offset by increased revenue from the Company’s collaboration with Gilead and increased contract manufacturing revenue.
R&D Expenses: Research and development expenses were $51.7 million for the quarter ended June 30, 2024, compared to $43.2 million for the quarter ended June 30, 2023. The increase was primarily due to manufacturing and IND-enabling costs related to MGC028.
SG&A Expenses: Selling, general and administrative expenses were $14.4 million for the quarter ended June 30, 2024, compared to $13.7 million for the quarter ended June 30, 2023.
Net Income (Loss): Net loss was $55.7 million for the quarter ended June 30, 2024, compared to net income of $57.5 million for the quarter ended June 30, 2023. Net income for the quarter ended June 30, 2023 included approximately $100.0 million as a component of Other Income related to the sale of the Company’s single-digit royalty interest on global net sales of TZIELD (teplizumab-mzwv) to DRI Healthcare Acquisitions LP in March 2023.
Shares Outstanding: Shares of common stock outstanding as of June 30, 2024 were 62,720,969.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities balance of $140.4 million as of June 30, 2024, plus the $100.0 million in milestones subsequently received from Incyte, in addition to projected and anticipated future payments from partners and product revenues should support its cash runway into 2026. The Company’s expected funding requirements reflect anticipated expenditures related to the Phase 2 TAMARACK clinical trial, the Phase 2 LORIKEET study as well as MacroGenics’ other ongoing clinical and preclinical studies.
No Conference Call

Given the embargoed TAMARACK data being presented at the upcoming ESMO (Free ESMO Whitepaper) presentation, the Company’s management has entered a quiet period and will not be hosting a conference call to discuss its financial results or corporate progress for the quarter ended June 30, 2024. The Company intends to resume its quarterly results conference calls in the future.

On August 6, 2024 Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, reported receipt of a "Study May Proceed" letter from the U.S. Food and Drug Administration ("FDA") for the initiation of a Phase I/II clinical study of Silmitasertib (CX-4945) for the treatment of children and young adults with relapsed refractory solid tumors (Press release, Senhwa Biosciences, AUG 6, 2024, View Source [SID1234645442]).

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The principal investigator of this investigator-initiated trial (IIT), Dr. Giselle Saulnier Sholler, is an internationally known pediatric hematology-oncology clinician and researcher. In August 2023, she was invited to serve as the division chief of Pediatric Hematology and Oncology at Penn State Health Children’s Hospital. She brought with her the Beat Childhood Cancer Research Consortium, a worldwide network of more than 55 universities and children’s hospitals dedicated to discovering new therapies and cures for children with cancer.

The research consortium has enrolled more than 1,800 pediatric cancer patients in more than 23 trials, and has previously helped a drug obtain FDA approval for high-risk relapsed neuroblastoma treatments. This phase I/II study is funded by the Four Diamonds Foundation, with Senhwa Biosciences providing the investigational drug, Silmitasertib (CX-4945).

Senhwa Biosciences is planning to apply for Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation (RPD) for Silmitasertib (CX-4945) for the treatment of neuroblastoma. If these designations are granted and the drug is successfully commercialized, the company would obtain a Priority Review Voucher (PRV). The holder of a PRV can designate any future human drug application to receive priority review, potentially shortening the review time to 6 months, which could accelerate the timeline for the company (or its partners) to bring other products to market.

The clinical trial design also includes Ewing’s sarcoma and osteosarcoma, which are common pediatric bone cancers with poor prognoses, representing unmet medical needs.