Biotheus Enters Into Strategic Partnership with BioNTech to Develop and Commercialize Bispecific Antibody Candidate Targeting PD-L1 and VEGF in Multiple Solid Tumor Indications

On November 6, 2023 Biotheus Inc. ("Biotheus"), a clinical-stage biotech company dedicated to the discovery and development of biologics for oncology and inflammatory diseases, reported that the company has entered into an exclusive global license and collaboration agreement under which BioNTech will be developing, manufacturing and commercializing PM8002 globally ex-Greater China, whereas Biotheus retains the rights to exploit PM8002 in Greater China (Press release, Biotheus, NOV 6, 2023, View Source [SID1234637070]). PM8002 is currently being tested in Phase 2 studies in China to evaluate the efficacy and safety of the candidate as a monotherapy or in combination with chemotherapy in patients with advanced solid tumors.

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Under the terms of the agreement, Biotheus will receive an upfront payment of $55 million, and is eligible to receive additional development, regulatory and sales milestone payments potentially totalling over $1 billion as well as tiered royalties on potential future product sales. The transaction is expected to close in Q4 2023, subject to customary closing conditions, including clearance under the Hart-Scott-Rodino ("HSR") Antitrust Improvements Act, and regulatory clearances.

PM8002 is a bispecific antibody candidate with humanized anti-PD-L1 single heavy-chain variable (VHH) domains fused to an anti-VEGF-A IgG1 antibody containing Fc-silencing mutations. PM8002 has demonstrated a positive safety profile and encouraging antitumor activity presumably through reduced systemic toxicity by enriching anti-VEGF activity into the tumor microenvironment at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting and ESMO (Free ESMO Whitepaper) Congress 2023.

"Biotheus’ innovative platform has the capability to expedite preclinical research, bolstering our impressive innovative pipeline of products with encouraging efficacy and safety including PM8002. Collaborating with industry trailblazer BioNTech, we hope to advance PM8002 through multi-regional clinical trials with the aim to be able to provide it to patients worldwide," stated Xiaolin Liu, Co-founder, Chairman, and CEO of Biotheus.

Landmark Bio Signs Multi-Year Agreement to Manufacture Galapagos’ Oncology CAR-T Cell Therapy Clinical Programs at the Point-of-Care

On November 6, 2023 Landmark Bio, a collective endeavor bringing together leaders in industry, academia, and research hospitals to accelerate development and industrialization of next-generation genomic medicines, reported that it has signed a multi-year strategic manufacturing agreement with Galapagos NV (Euronext & NASDAQ: GLPG), an innovative biotech company with operations in Europe and the U.S (Press release, Landmark Bio, NOV 6, 2023, View Source [SID1234637069]).

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Under the terms of the agreement, Landmark Bio will perform GMP manufacturing of clinical trial batches of Galapagos’ development programs of chimeric antigen receptor (CAR) T-cell therapies in hematology-oncology in the Boston metropolitan area.

The manufacturing agreement aims at implementing Galapagos’ novel decentralized CAR-T manufacturing model, designed to enable clinicians to administer CAR T-cells within a median of seven days of leukapheresis, thereby aiming to address important limitations of current CAR-T treatments.

"We are excited to partner with Galapagos to support their CAR-T clinical development programs in the U.S.," said Ran Zheng, CEO of Landmark Bio. "This strategic manufacturing collaboration is a testament to our expertise in cell and gene therapy manufacturing and underscores our commitment to bring more life-saving therapies to patients faster."

Landmark Bio’s 44,000 square-foot fully integrated development and manufacturing facility includes laboratory space for translational research and early development, process and analytical development, and technology innovation. The biomanufacturing area is comprised of nine cleanrooms for cell therapies, genome editing, viral vector, mRNA, and lipid nanoparticle production as well as fill and finish and in-house Quality Control (QC) testing. In addition, Landmark Bio provides wraparound services such as drug development and regulatory consulting, program management and other support services.

Financial terms of the agreement were not disclosed.

Verastem Oncology Announces Efficacy and Safety Data of Avutometinib and Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) in Heavily Pretreated Patient Population

On November 6, 2023 Verastem Oncology (Nasdaq: VSTM) (the "Company"), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported results of the efficacy and safety of avutometinib and defactinib in recurrent low-grade serous ovarian cancer (LGSOC) following prior systemic therapy (Press release, Verastem, NOV 6, 2023, View Source [SID1234637068]). The results of this planned subgroup analysis of Part A of the Phase 2 RAMP 201 (ENGOT-ov60/GOG-3052) trial were presented as a late-breaking abstract in an oral presentation during a plenary session at the Annual Global Meeting of the International Gynecologic Cancer Society (IGCS 2023) November 5-7, 2023, in Seoul, Korea.

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"Patients with recurrent LGSOC currently have no medicines approved by the U.S. Food and Drug Administration and limited treatment options for their disease," said Rachel Grisham, M.D., Section Head, Ovarian Cancer and Director, Westchester Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center N.Y., and the lead U.S. investigator of RAMP 201. "The results from this analysis are encouraging as the combination of avutometinib and defactinib demonstrates robust efficacy in recurrent LGSOC irrespective of the number of prior therapies, and for most of which, response to previous therapy was poor."

This planned subgroup analysis was performed to assess efficacy (confirmed objective response rate (ORR) via blinded independent central review per RECIST v1.1) and safety in prior lines of therapy (LoT) (1-3 LoT, ≥4 LoT). The analysis also evaluated efficacy in the context of best response to most recent prior treatment in the metastatic/recurrent setting.

In the combination arm, the observed ORRs were consistent across patients who received 1-3 (45.5%, 5/11, 95% CI 17-77) and ≥4 lines of therapy (44.4%, 8/18, 95% CI 22-69). Prior to enrollment in RAMP 201, only 2/23 (8.7%) patients responded to their last prior treatment in the metastatic/recurrent setting, whereas the combination of avutometinib and defactinib yielded an ORR of 43.5% (10/23) in this subgroup. The safety profiles of avutometinib and defactinib were similar in the less and more heavily pretreated subgroups and both analyses were consistent with previously reported safety data. The majority of treatment-emergent adverse events were mild to moderate.

Initial results of RAMP 201 Part A, presented at the American Society for Clinical Oncology Annual Meeting in May 2023, demonstrated an ORR of 45% (13/29) and tumor shrinkage in 86% (25/29) of evaluable patients that were treated with the combination of avutometinib and defactinib. Safety and tolerability were favorable and consistent with previously reported data. As previously announced, Verastem Oncology intends to file for accelerated approval with the FDA for the combination of avutometinib and defactinib based on mature data from the RAMP 201 trial, together with the results of the investigator-initiated FRAME trial. The Company plans to initiate its Phase 3 confirmatory trial (RAMP 301) of avutometinib and defactinib in LGSOC versus standard of care (SOC) chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole) before the end of the year.

Dr. Grisham is a paid consultant for Verastem Oncology.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 301 is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization and expansion phases and is enrolling for low-dose evaluation. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the "Therapeutic Accelerator Award" Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.

Autolus Therapeutics announces participation in upcoming conferences

On November 6, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its participation in three upcoming conferences in November (Press release, Autolus, NOV 6, 2023, View Source [SID1234637067]).

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Truist Securities BioPharma Symposium
Panel: Considerations for an Oncology Company’s Autoimmune Side Hustle
Date and time: 9 November 2023, 11:40am ET / 16:40pm GMT
Location: New York, USA
Presenter: Dr Christian Itin, Chief Executive Officer, Autolus Therapeutics

Jefferies London Healthcare Conference
Fireside Chat
Date and time: 16 November 2023, 4:00am ET / 9:00am GMT
Location: London, UK
Presenter: Dr Christian Itin, Chief Executive Officer, Autolus Therapeutics

Piper Sandler 35th Annual Healthcare Conference
Fireside Chat
Date and time: 28 November 2023, 11:30am ET/ 16:30pm GMT
Location: New York, USA
Presenter: Dr Christian Itin, Chief Executive Officer, Autolus Therapeutics

Find out more information about upcoming events and any webcast and replay details at: View Source

Krystal Biotech Announces Third Quarter 2023 Financial Results and Provides Business Update

On November 6, 2023 Krystal Biotech, Inc. (the "Company") (NASDAQ: KRYS), a commercial-stage biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs, reported financial results and key business updates for the third quarter ended September 30, 2023 (Press release, Krystal Biotech, NOV 6, 2023, View Source [SID1234637066]).

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"The third quarter was highlighted by strong commercial execution of the VYJUVEK launch, advancement of the oncology program into the clinic and continued momentum in the CF program," said Krish S. Krishnan, Chairman and CEO of Krystal Biotech. "With respect to the VYJUVEK launch, our guiding vision is centered around optimizing the patient experience, and we have and will continue to work tirelessly to ensure that each patient’s journey, with respect to starting on VYJUVEK and staying on it, is smooth, timely and hassle free."

VYJUVEK
(beremagene geperpavec-svdt, or B-VEC)

For the treatment of Dystrophic Epidermolysis Bullosa (DEB)

The Company received 284 Patient Start Forms from 136 unique prescribers as of the end of the third quarter of 2023:

20% of the start forms were generated from patients with dominant DEB;

33% of the start forms were from patients 10 years of age or younger; and

Patient compliance on VYJUVEK is currently tracking at 96%.
The Company has received positive coverage determinations from all major commercial national health plans. Optional Medicaid fee-for-service states initiated coverage in July. The Company expects to receive positive coverage from most mandatory states in the fourth quarter of 2023 and the balance in the first quarter of 2024.

In October, the Company filed for a Marketing Authorization for B-VEC with the European Medical Agency and anticipates approval in the EU in the second half of 2024.

Following acceptance of the open label extension study of B-VEC by Japan’s Pharmaceuticals and Medical Devices Agency in July 2023, the Company initiated the extension study and dosed 5 patients. Following completion of the open label extension study, the Company intends to file a Japanese New Drug Application for B-VEC for DEB in the first half of 2024. Details of the trial can be found at View Source under JRCT ID jRCT2053230075.
Respiratory

KB407 for the treatment of Cystic Fibrosis (CF)

Cohort 1 of the Phase 1 (CORAL-1) study has been enrolled and completed. No severe or serious adverse events were observed in patients treated in Cohort 1 of the CORAL-1 study. We are working to initiate Cohort 2 of the CORAL-1 study following safety review by the Data Monitoring Committee. The CORAL-1 study is a multi-center, dose-escalation trial of KB407 in patients with CF, regardless of their underlying genotype. The Company anticipates announcing data from the Phase 1 study in 2024. Details of the Phase 1 study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837.
KB408 for the treatment of Alpha-1 Antitrypsin Deficiency (AATD)

In September, the Company announced that the U.S. Food and Drug Administration (FDA) had cleared the Company’s Investigational New Drug (IND) application for KB408 for the treatment of AATD and granted KB408 Orphan Drug Designation. The Company expects to dose the first patient in a Phase 1 clinical trial (SERPINA-1) in the first quarter of 2024.
Oncology

KB707 for the treatment of solid tumors

In October, the first patient was dosed in the Phase 1 (OPAL-1) study to evaluate intratumoral KB707 in patients with locally advanced or metastatic solid tumor malignancies. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT05970497.

The Company presented preclinical data in multiple oncology models at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s annual meeting on November 3 and 4, 2023. Combinatorial IL-2 and IL-12 expressed from the Company’s platform technology was shown in one presentation, to provide a synergistic effect in a melanoma model, suppressing treated and non-treated tumor outgrowth, enhancing survival, and eliciting a durable memory response sufficient for recurrent tumor control. Similarly, the Company presented that non-invasive inhalation of vector-encoded IL-2 and IL-12 was found to be both safe and effective in treating lung tumors in a metastasis model, resulting in long-term survival after single or repeated cancer cell challenge, suggestive of prolonged adaptive immunity.

The Company is on track to file an amendment to the existing KB707 IND in the fourth quarter of 2023 to allow the Company to evaluate inhaled KB707 in a clinical trial to treat tumors in a patient’s lungs. The Company expects to dose the first patient with inhaled KB707 in the first half of 2024.

In October, the United States Patent & Trademark Office issued to the Company U.S. Patent No. 11,779,660 entitled Viral Vectors for Cancer Therapy.
Dermatology

The Company remains on track to commence the Phase 2 cohort of its KB105-02 (JADE-1) trial for the treatment of TGM1-ARCI in 2024 and plans to file an IND application with the FDA and to initiate a clinical trial of KB104 to treat patients with Netherton Syndrome in late 2024.
Aesthetics

KB301 for the treatment of aesthetic indications

In April, Jeune Aesthetics, Inc., a wholly-owned subsidiary of the Company, announced the dosing of the first subject in the Phase 1, Cohort 3 study of KB301 for the improvement of lateral canthal lines at rest. The study is on-going, and the Company plans to announce results from this study in the first half of 2024. Details of the Phase 1 study can be found at www.clinicaltrials.gov under NCT identifier NCT04540900.
Business

In August, the Company sold its Rare Pediatric Disease Priority Review Voucher (PRV) for $100 million. The Company was awarded the PRV in connection with the FDA’s accelerated approval of VYJUVEK for the treatment of DEB for patients 6 months of age and older.

In August, the Company began research and development operations in its second commercial scale CGMP biologics manufacturing facility, ASTRA, a 155,000 sq. ft. state-of-the-art CGMP facility with comprehensive end-to-end capabilities.

Financial results for the quarter ended September 30, 2023:

Cash, cash equivalents, and investments totaled $598.6 million on September 30, 2023.
The Company recorded its first sales for patients that began treatment in August 2023 and the resulting product revenues, net totaled $8.6 million for the quarter ended September 30, 2023.
Cost of goods sold totaled $223 thousand for the quarter ended September 30, 2023. Prior to receiving FDA approval for VYJUVEK in May 2023, costs associated with the manufacturing of VYJUVEK were expensed as research and development expense. As such, a portion of the cost of inventory sold during the period was expensed prior to FDA approval.
The Company recorded a gain of $100 million for the sale of the rare pediatric disease Priority Review Voucher.
Research and development expenses for the quarter ended September 30, 2023 were $10.6 million, inclusive of $2.3 million of stock-based compensation, compared to $11.5 million, inclusive of stock-based compensation of $2.2 million for the quarter ended September 30, 2022.
Selling, general, and administrative expenses for the quarter ended September 30, 2023 were $23.7 million, inclusive of stock-based compensation of $6.0 million, compared to $19.9 million, inclusive of stock-based compensation of $6.9 million, for the quarter ended September 30, 2022.
Net income (loss) for the quarters ended September 30, 2023 and 2022 was $80.7 million and $(29.9) million, or $2.88 and $(1.17), respectively, per common share (basic) and $2.79 and $(1.17), respectively per common share (diluted).
For additional information on the Company’s financial results for the quarter ended September 30, 2023, please refer to the Form 10-Q filed with the SEC.
Financial results for the nine months ended September 30, 2023:

The Company recorded its first sales for patients that began treatment in August 2023 and the resulting product revenues, net totaled $8.6 million for the nine months ended September 30, 2023.
Cost of goods sold totaled $223 thousand for the nine months ended September 30, 2023. Prior to receiving FDA approval for VYJUVEK in May 2023, costs associated with the manufacturing of VYJUVEK were expensed as research and development expense. As such, a portion of the cost of inventory sold during the period was expensed prior to FDA approval.
The Company recorded a gain of $100 million for the sale of the rare pediatric disease Priority Review Voucher.
Research and development expenses for the nine months ended September 30, 2023 were $35.1 million, inclusive of stock-based compensation of $7.7 million, compared to $31.7 million, inclusive of stock-based compensation of $5.5 million for the nine months ended September 30, 2022.
Selling, general, and administrative expenses for the nine months ended September 30, 2023 were $73.6 million, inclusive of stock-based compensation of $22.4 million, compared to $53.7 million, inclusive of stock-based compensation of $18.1 million for the nine months ended September 30, 2022.
Net income (loss) for the nine months ended September 30, 2023 and 2022 were $2.2 million and $(107.9) million, or $0.08 and $(4.24), respectively, per common share (basic) and $0.08 and $(4.24), respectively, per common share (diluted).
For additional information on the Company’s financial results for the nine months ended September 30, 2023, please refer to the Form 10-Q filed with the SEC.
Conference Call

Krystal Biotech will host a conference call to discuss its third quarter 2023 financial results and business highlights today, November 6, 2023, at 8:30 a.m. ET. To access the live call, please preregister: View Source;confId=57029.

A replay of the conference call will be available on the Investors section of the Company’s website at View Source for 30 days following the event.