Aptevo Therapeutics Presenting at The Protein & Antibody Engineering Summit, Boston, MA

On May 14, 2024 Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported a presentation at The Essential Protein & Antibody Engineering Summit (PEGS) conference in Boston MA (Press release, Aptevo Therapeutics, MAY 14, 2024, View Source [SID1234643260]). The session, being offered today, Tuesday May 14, 2023 at 8:30 AM Eastern time and entitled "Development of Target Activated ADAPTIRs for Tumor Immunotherapy," will be led by Dr. Peter Pavlik, PhD, Senior Director of Protein Engineering at Aptevo and will focus on the strategic deployment of early functional screening of a diverse group of binding domains against a given target, combined with screening in multiple possible final formats to elicit varied functional activity, exemplified by preclinical and clinical data supporting predictive outcomes.

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"As a Company, Aptevo is focused on innovations in bispecific cancer therapeutics. We are excited to present at PEGS and share key learnings and expertise with a like-minded community," said Peter Pavlik, PhD, Senior Director, Protein Engineering at Aptevo. He continued, "As we have developed our portfolio of two clinical (APVO436 and ALG.APV-527) and three preclinical candidates (APVO603, APVO711 and APVO442), we have purposefully deployed engineering strategies intended to produce safe and efficacious drug candidates and our outcomes in both the clinic and the lab to date suggest that this approach is successful."

Aptevo continues to add to a growing body of clinical evidence that supports the preclinical predications of safety, conditional activation, and clinical activity of its portfolio of assets. Recent news from the Company’s two clinical programs includes:

A heavily pretreated breast cancer patient, enrolled in the ALG.APV-527 Phase 1 open-label, multi-center, multi-cohort trial for the treatment of multiple solid tumor types, entered the trial and improved from progressive disease to long-lasting stable disease (SD) while on therapy. The patient has remained on study for more than eleven months and been successfully transitioned to a higher dose level, with no new adverse events since the transition, which may allow for increased clinical benefit. The trial is more than 50% enrolled and we are dosing cohort 5
The Company is on track to initiate part 1 of its upcoming dose optimization trial in 2Q 2024. The study will further evaluate APVO436 for the treatment of acute myeloid leukemia (AML). Aptevo has partnered with premier CRO, Prometrika, for the upcoming study. The first part is a dose optimization trial evaluating standard of care venetoclax + azacitidine along with APVO436 as a frontline treatment for AML patients. It is planned as an open-label, multi-center, multi-cohort study. The trial will evaluate safety/tolerability and efficacy of the triplet combination at multiple dose levels

About Dr. Pavlik
Peter Pavlik is Senior Director of Protein Engineering at Aptevo Therapeutics. He has been working on bispecific antibody development at Aptevo for the last 8 years, focusing on discovery of new binding domains, their engineering into bispecific molecules, optimization of developability, and engineering of manufacturing cell lines. Before joining Aptevo, Peter worked for 8 years at MedImmune/AstraZeneca on antibody discovery and protein engineering and for 10 years at Los Alamos National Labs developing antibody discovery technologies at a genome scale. Peter obtained M.Sc. in Biochemistry from Comenius University in Slovakia and Ph.D. in Biochemistry from the University of Vienna in Austria.

Precigen Reports First Quarter 2024 Financial Results and Business Updates

On May 14, 2024 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported first quarter 2024 financial results and business updates (Press release, Precigen, MAY 14, 2024, View Source [SID1234643254]).

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"We are excited to share the pivotal Phase 2 data for our PRGN-2012 study in patients with RRP at ASCO (Free ASCO Whitepaper) and look forward to providing additional details regarding the results at our planned conference call following the presentation. We remain on track for a PRGN-2012 rolling BLA submission in the second half of 2024 and we are actively moving ahead with our commercial readiness efforts in anticipation of a potential launch of PRGN-2012 in 2025," said Helen Sabzevari, PhD, President and CEO of Precigen. "Based on the competitive advantages of PRGN-2012, including a favorable route of administration, safety profile and the efficacy demonstrated in the clinical trial results so far, we believe, PRGN-2012 has the potential to be the first-in-class and best-in-class treatment for RRP patients. We anticipate PRGN-2012 to overwhelmingly be the treatment of choice for RRP patients, if approved, as indicated by our commissioned research of healthcare providers and key opinion leaders which found PRGN-2012’s competitive advantages highly compelling."

"With multiple milestones anticipated in 2024 and 2025, we remain steadfastly committed to a strategy of sound financial management," said Harry Thomasian Jr., CFO of Precigen. "We are evaluating various financing opportunities to strengthen our balance sheet as we prepare our lead asset, PRGN-2012, for potential commercial launch in 2025."

Key Program Highlights

AdenoVerse

· PRGN-2012 in RRP: PRGN-2012 is an investigational off-the-shelf AdenoVerse gene therapy designed to elicit immune responses directed against cells infected with human papillomavirus (HPV) 6 or HPV 11 for the treatment of recurrent respiratory papillomatosis (RRP). PRGN-2012 was the first to receive Breakthrough Therapy Designation and an accelerated approval pathway for RRP from the FDA. PRGN-2012 received Orphan Drug Designation from the US Food and Drug Administration (FDA) and Orphan Drug Designation from the European Commission.

o PRGN-2012 is currently under investigation in a Phase 1/2 pivotal single-arm study in adult patients with RRP (clinical trial identifier: NCT04724980).

o Results from the Phase 1 portion of the Phase 1/2 study were published in the peer-reviewed journal, Science Translational Medicine, a leading publication from the American Association for the Advancement of Science (AAAS).

§ PRGN-2012 demonstrated overall safety and clinically meaningful benefit with 50% of patients (N=12) in Complete Response, which is defined as no surgeries needed during the 12-month period following PRGN-2012 treatment completion. All Complete Responses were durable and ongoing more than two years after PRGN-2012 treatment.

§ 83% of patients had a reduction in RRP surgeries in the 12-month period after PRGN-2012 treatment compared to 12 months pre-treatment.

§ Correlative data support expansion of peripheral HPV 6 and HPV 11–specific T cell immunological responses as the underlying mechanism of action for PRGN-2012.

o PRGN-2012 is built using the Company’s differentiated gorilla adenovector that allows for repeat dosing. The redosing potential of AdenoVerse has been highlighted in clinical studies where repeat administrations of PRGN-2009 and PRGN-2012 gene therapies led to enhancement of antigen-specific T cell immune responses without generation of significant neutralizing antibodies in contrast to other viral vectors.

o Results from the pivotal Phase 2 study of PRGN-2012 for the treatment of RRP, including immunological responses, will be presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in a late-breaking oral presentation titled, "PRGN-2012, a novel gorilla adenovirus-based immunotherapy, provides the first treatment that leads to complete and durable responses in recurrent respiratory papillomatosis patients." Scott M. Norberg, DO, Associate Research Physician, Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, will deliver the presentation on June 3, 2024 at 8:30 AM CT.

o The Company plans to host a conference call on June 3, 2024 to discuss in detail the PRGN-2012 pivotal study results presented and provide business updates.

o FDA confirmed that the ongoing Phase 1/2 single arm study will serve as pivotal and no additional randomized, placebo-controlled trial will be required to support submission of a Biologics License Application (BLA). A rolling BLA submission under an accelerated approval pathway is anticipated in the second half of 2024. Based on FDA guidance, the Company is on track to initiate a confirmatory study prior to submission of the BLA.

o Commercial readiness preparations are underway for a potential launch in 2025.

o The Company and the Recurrent Respiratory Papillomatosis Foundation will co-sponsor the inaugural RRP Awareness Day on June 11, 2024. The multi-stakeholder event will raise awareness and bring together individuals living with RRP, caregivers, clinicians, and government officials to encourage new connections and build community among those interested in and affected by RRP. The inaugural event will be hybrid with in-person participation at the National Press Club in Washington DC and a webcast for virtual participation.

· PRGN-2009 in OPSCC and Cervical Cancer: PRGN-2009 is an investigational off-the-shelf AdenoVerse gene therapy designed to activate the immune system to recognize and target HPV-associated cancers.

o The Phase 2 study of PRGN-2009 in combination with pembrolizumab in newly diagnosed patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is enrolling patients (clinical trial identifier: NCT05996523).

§ An abstract titled, "Phase II trial of immunotherapeutic HPV vaccine PRGN-2009 with pembrolizumab before standard treatment in subjects with newly diagnosed HPV-associated oropharyngeal cancer" will be presented as a trial-in-progress poster presentation on June 2, 2024 from 9:00 AM to 12:00 PM CT at ASCO (Free ASCO Whitepaper).

o The Phase 2 randomized, open-label study of PRGN-2009 in combination with pembrolizumab in patients with HPV-associated recurrent/metastatic cervical cancer is active and recruiting patients (clinical trial identifier: NCT06157151).

§ An abstract titled, "A Phase 2 study to evaluate efficacy and safety of PRGN-2009, a novel gorilla adenovirus-based immunotherapy, in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer" will be presented as a trial-in-progress poster presentation on June 3, 2024 from 9:00 AM to 12:00 PM CT at ASCO (Free ASCO Whitepaper).

UltraCAR-T

· PRGN-3006 in AML/MDS: PRGN-3006 is an investigational multigenic, autologous chimeric antigen receptor T cell (CAR-T) therapy engineered to simultaneously express a CAR specifically targeting CD33, membrane bound IL-15 (mbIL15), and a safety/kill switch. PRGN-3006 has been granted Orphan Drug Designation in patients with acute myeloid leukemia (AML) and Fast Track Designation in patients with relapsed/refractory (r/r) AML by the FDA.

o PRGN-3006 is currently under investigation in a Phase 1b dose expansion clinical trial (clinical trial identifier: NCT03927261) for the treatment of patients with r/r AML or higher-risk myelodysplastic syndromes (MDS).

o An interim Phase 1b dose expansion data presentation is anticipated in the second half of 2024.

o PRGN-3005 in Ovarian Cancer: PRGN-3005 is an investigational multigenic, autologous CAR-T cell therapy engineered to express a CAR specifically targeting the unshed portion of MUC16, mbIL15, and a safety/kill switch.

o The Phase 1b dose expansion portion of the Phase 1/1b study is ongoing (clinical trial identifier: NCT03907527).

o PRGN-3007 in Advanced ROR1+ Hematological and Solid Tumors: PRGN-3007, based on the next generation UltraCAR-T platform, is an investigational multigenic, autologous CAR-T cell therapy engineered to express a CAR targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), mbIL15, a safety/kill switch, and a novel mechanism for the intrinsic blockade of PD-1 gene expression.

o The Phase 1 dose escalation portion of the Phase 1/1b study is ongoing (clinical trial identifier: NCT05694364).

o A preliminary Phase 1 dose escalation data presentation is anticipated by the end of 2024.

Financial Highlights

o Cash, cash equivalents, and short-term investments totaled $44.8 million as of March 31, 2024.

o Selling, general, and administrative (SG&A) costs decreased 13% compared to the three months ended March 31, 2023.

o Property, plant, and equipment, net, increased $5.5 million from December 31, 2023 primarily due to the build-out of our cGMP manufacturing facility.

First Quarter 2024 Financial Results Compared to Prior Year Period

Research and development expenses increased $2.1 million, or 17%, compared to the three months ended March 31, 2023. Salaries, benefits, and other personnel costs increased $1.5 million due to an increase in the hiring of employees throughout 2023 to support the growth in the Company’s clinical development activities as well as increased fees paid to consultants and contract research organizations in the first quarter of 2024 compared to the same period in 2023.

SG&A expenses decreased $1.5 million, or 13%, compared to the three months ended March 31, 2023, primarily driven by a reduction in stock compensation and insurance expenses in the first quarter of 2024 compared to same period in 2023. In addition, the costs associated with PRGN-2012 commercial readiness increased compared to the same period in 2023.

Total revenues decreased $0.8 million, or 43%, compared to the three months ended March 31, 2023. This decrease was due to the reduction in products and services performed at Exemplar. Gross margin on product and services also declined in the current period primarily as a result of the decreased revenues at Exemplar.

Net Loss was $23.7 million, or $(0.10) per basic and diluted share, compared to net loss of $22.7 million, or $(0.10) per basic and diluted share, in period ended March 31, 2023.

Celularity Data Published in Journal for ImmunoTherapy of Cancer Reveals Benefits of Placental Circulating T Cells for CAR-T Therapy

On May 14, 2024 Celularity Inc. (NASDAQ: CELU) ("Celularity"), a regenerative and cellular medicine company developing placental-derived allogeneic cell therapies and advanced biomaterial products, reported that the Journal for ImmunoTherapy of Cancer, a peer-reviewed online journal of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), published data highlighting the potential advantages of Celularity’s T-Cell platform for future immunotherapies including chimeric antigen receptor (CAR-T) therapies (Press release, Celularity, MAY 14, 2024, View Source [SID1234643253]).

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The data compared CAR-T cells derived from Celularity’s proprietary T cell platform with CAR-T cells derived from healthy adult peripheral blood mononuclear cells (PBMCs). CAR-T cells generated from its T-Cell platform retained stemness, maintained longer telomeres, and were more resistant to both exhaustion and immune checkpoint upregulation. Additionally, an attenuated cytokine response was observed without loss of cytotoxicity. This translated into improved and prolonged in vivo efficacy and persistence compared with healthy, adult PBMC-derived CAR-T.

"These findings help differentiate the placenta as a source of cells for immunotherapy and demonstrate the valuable potential of our placental platform for allogeneic CAR-T products," said Dr. Robert Hariri, founder, Chairman and CEO of Celularity. "As the field of cellular immunotherapy moves towards delivering ‘one-size-fits-all’ allogeneic products, the stemness advantages inherent in our platform have the potential to translate into improved persistence and durable activity with an enhanced safety profile, offering promising prospects for developing more effective CAR-T therapies in the future. Moreover, we believe that our placental platform offers a level of scalability and consistency in manufacturing which can significantly impact the economics of delivering these therapies in the future. Through our state-of-the-art manufacturing and technical infrastructure, Celularity can be an ideal development and manufacturing partner in the cellular medicine industry."

BridgeBio Pharma to Participate in the Bank of America Merrill Lynch Global Healthcare Conference 2024

On May 14, 2024 BridgeBio Pharma, Inc. (Nasdaq: BBIO) ("BridgeBio" or the "Company"), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported that members of its management team will present at the Bank of America Merrill Lynch Global Healthcare Conference 2024 in Las Vegas, NV on Wednesday, May 15 at 3:00 pm PT (Press release, BridgeBio, MAY 14, 2024, View Source [SID1234643252]).

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To access the live webcast of BridgeBio’s presentation, please visit the "Events & Presentations" page within the Investors section of the BridgeBio website at View Source A replay of the webcast will be available on the BridgeBio website for 90 days following the event.

Bolt Biotherapeutics Reports First Quarter 2024 Results, Announces Strategic Pipeline Prioritization and Changes to Leadership Team

On May 14, 2024 Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, reported financial results for the first quarter ended March 31, 2024 and announced a strategic prioritization as well as changes to its leadership team (Press release, Bolt Biotherapeutics, MAY 14, 2024, View Source [SID1234643251]). The company will focus its pipeline on its first-in-class proprietary agonist antibody targeting Dectin-2 and its next-generation BoltbodyTM ISAC programs, continue to support its collaborations with Genmab and Toray, and reduce its workforce by approximately 50%. This will extend cash runway into the second half of 2026.

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As part of this refocusing, Willie Quinn has been appointed Chief Executive Officer. Grant Yonehiro has been promoted to Chief Operating Officer, Dawn Colburn, Pharm.D. has been promoted to Senior Vice President, Clinical Development. Michael Alonso, Ph.D. has been promoted to Senior Vice President, Research and Sarah Nemec is being appointed Principal Accounting Officer.

"At Bolt, we set a high bar for advancing our programs, and while BDC-1001 provided clinical validation for the ISAC mechanism, it did not meet our high bar for advancement. With limited resources, we want to focus those resources on the best product candidates. Our BoltbodyTM ISAC technology platform continues to improve and our next-gen ISACs have outperformed cytotoxic ADCs in our preclinical studies. The increased activity of the next-gen BoltbodyTM ISACs is opening the door to tumor targets with lower expression, while maintaining design choices that prioritize safety. With this in mind, we have decided to discontinue all BDC-1001 development and focus resources on BDC-3042 and BDC-4182, our next-gen ISAC targeting the clinically validated cancer antigen Claudin 18.2," said Willie Quinn, Chief Executive Officer. "We believe that BDC-3042, a first-in-class agonist antibody that reawakens myeloid cells to attack tumor cells, has broad potential across many tumor types. We’ve seen encouraging safety to date in our Phase 1 dose escalation study of BDC-3042 and are excited about the very strong preclinical data for BDC-4182. We believe focusing on these programs will deliver significant value to shareholders. In conjunction, we are streamlining our operations to align resources and extend our cash runway to support these programs through key value inflection points."

"Over the last several years, Bolt has leveraged our expertise to create BoltbodyTM ISACs with optimized tumor-targeting antibodies and stronger payloads that have the potential to deliver superior efficacy while maintaining an acceptable safety profile," said Michael Alonso, Senior Vice President, Research. "We are excited to advance our first next-generation Boltbody ISAC, BDC-4182, as Bolt’s next clinical candidate and to unveil Claudin 18.2 as the target antigen for this agent. BDC-4182 has advanced into IND-enabling studies and we look forward to sharing more details soon."

Recent Highlights and Anticipated Milestones


BDC-3042 Phase 1 dose escalation continues to advance. BDC-3042, a proprietary agonist antibody that targets Dectin-2, an immune activating receptor expressed by tumor-associated macrophages (TAMs), has advanced through the first 3 dose escalation cohorts of the Phase 1 trial without any dose-limiting toxicities, and the fourth dose level cohort is fully enrolled. BDC-3042 has been well tolerated in each of the cohorts to date. Bolt anticipates providing an update on enrollment and safety in the second half of the year.

Announced BDC-4182 as Bolt’s next-generation BoltbodyTM ISAC clinical candidate targeting Claudin 18.2. Claudin 18.2 is a novel, clinically validated target in oncology with programs in development for the treatment of gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. BDC-4182 has advanced into IND-enabling activities, supported by in vitro and in vivo experiments demonstrating potent anti-tumor activity in multiple preclinical models, some of which were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 2023 Annual Meeting in October.

Corporate Updates


Discontinued development of trastuzumab imbotolimod (BDC-1001). Following a strategic review, Bolt has determined that the program will not meet its pre-defined success criteria, and Bolt will therefore be focusing resources on its next-generation ISAC programs.

Leadership changes. Willie Quinn is being appointed Chief Executive Officer. Former officers Randall Schatzman, Ph.D. and Edith Perez, M.D. are moving into advisory roles with Bolt. Grant Yonehiro, currently Chief Business Officer, is being promoted to Chief Operating Officer. Sarah Nemec, Vice President Finance, is being appointed Principal Accounting Officer and Michael Alonso, Ph.D., a co-founder of the company, is being promoted to Senior Vice President, Research. Dawn Colburn, Pharm.D. is being promoted to Senior Vice President of Clinical Development. Dr. Colburn joined Bolt in 2023, bringing over two decades of experience in oncology clinical development. Prior to joining Bolt, she was Vice President of Clinical Science for Agenus and Arcus Biosciences, where she built and led the clinical science organization and the non-small cell lung cancer clinical development strategy at both organizations.

Workforce reduction. In conjunction with this strategic refocusing, the Company will be reducing its workforce by approximately 50%. As a result of these actions, Bolt expects to extend its cash runway into the second half 2026, funding the completion of the BDC-3042 Phase 1 trial and also enabling the delivery of clinical data for next-generation ISAC BDC-4182.

Mr. Quinn commented, "We sincerely thank our dedicated and talented employees, as well as the BDC-1001 investigators and patients, for all they’ve done to advance our mission to leverage the immune system for a better way to treat cancer. To our colleagues who will be leaving Bolt as part of this realignment, we wish you all the best in your future endeavors and thank you for your contributions in leading Bolt to where we are today."

First Quarter 2024 Financial Results


Collaboration Revenue – Collaboration revenue was $5.3 million and $1.8 million for the quarter ended March 31, 2024, and 2023, respectively. The increase in revenue for the comparative periods was due to increased activity in collaborations with Genmab and Toray Industries, Inc. as the Company fulfills its performance obligations, and the conclusion of its performance obligations for the Innovent collaboration. Bolt also recognized $4.7 million in Other Income as a result of concluding its collaboration with Innovent.


Research and Development (R&D) Expenses – R&D expenses were $16.5 million for the quarter ended March 31, 2024, compared to $14.6 million for the same quarter in 2023. The increase in R&D expenses was due to higher clinical trial expenses due to continued progress in our clinical trials for product candidates, higher research and development contract service expenses, and higher salary and related expenses, partially offset by lower manufacturing expenses related to timing of batch production of our product candidates.


General and Administrative (G&A) Expenses – G&A expenses were $5.8 million for the quarter ended March 31, 2024, compared to $5.6 million for the same quarter in 2023. The increase in G&A expenses was due to higher salary and related expenses and higher consulting and professional services expenses.


Loss from Operations – Loss from operations was $17.1 million for the quarter ended March 31, 2024, compared to $18.4 million for the same quarter in 2023.

Conference Call and Webcast Details

Bolt will host a conference call and webcast today, May 14, 2024, at 4:30 p.m. Eastern Time to discuss its strategic restructuring. The webcast can be accessed by clicking the link: View Source, and will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website. A replay of the webcast will be archived on the Company’s website for up to 30 days following the presentation. A more detailed presentation of the results will be made available on the Company’s website at www.boltbio.com.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform
Bolt Biotherapeutics’ Boltbody ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to reprogram the tumor microenvironment to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.