Mission Bio Develops Single-Cell Solution to Address Challenges in Genome Editing

On May 12, 2023 Mission Bio, the single-cell DNA and multi-omics company, reported the Tapestri Genome Editing Solution, an end-to-end product for genome editing analysis (Press release, Mission Bio, MAY 11, 2023, View Source [SID1234631612]). The product will be previewed next week at the American Society of Gene and Cell Therapy Conference (ASGCT) (Free ASGCT Whitepaper) 26th Annual Meeting. By enabling robust single-cell insights impacting both efficacy and safety, the solution will be a powerful analytical tool for developing the next generation of gene-edited therapies.

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The first CRISPR-modified therapy is now under regulatory review, and many similar cell-based therapies are expected to follow for multiple intractable diseases. However, genome editing can result in complex, heterogeneous mixtures of edits that make it challenging to apply a level of process control over genome-edited cell products. The Tapestri Genome Editing Solution addresses these challenges by measuring gene editing outcomes at single-cell resolution, capturing the co-occurrence of on- and off-target edits, as well as the zygosity of edits, which conventional bulk analyses cannot. Additionally, this analysis can be completed within days by processing thousands of cells at a time without any prior selection, while conventional analytical methods require months for clonal outgrowth.

An early iteration of the Tapestri Genome Editing Solution is currently being tested by key genome editing researchers and leading cell therapy developers in academia and industry, who are providing vital feedback on the analysis. Mission Bio recently collaborated with the National Institute of Standards and Technology (NIST) in the Genome Editing Consortium, which provided qualified samples to collaborators to assess technologies that report variant size and frequency within a mixed cell population. Samantha Maragh, NIST Genome Editing Program Leader, will present results of the study at 12:00 p.m. PT on May 17 (Poster 533) at the ASGCT (Free ASGCT Whitepaper) Annual Meeting.

"We look forward to pulling back the curtain on our end-to-end Genome Editing Solution at ASGCT (Free ASGCT Whitepaper)," said Todd Druley, MD, PhD, Chief Medical Officer at Mission Bio. "The data acquired under the Genome Editing Consortium further demonstrates the Tapestri Platform’s potential as a standard analysis tool within the genome editing community. Given the heterogeneous results of gene editing strategies, there is a great need to address both industry and regulatory genome editing concerns with a consistent and highly precise technology for accurately measuring gene editing outcomes, and our new offering will be a complete solution to do just that."

The Tapestri Genome Editing Solution will be released later this year.

For more information about the Tapestri Genome Editing Solution, visit Mission Bio’s booth (#820) at ASGCT (Free ASGCT Whitepaper).

To learn more about Mission Bio and the Tapestri Platform, please visit www.missionbio.com.

Protagonist Therapeutics Announces Presentations at the 2023 Annual Congress of the European Hematology Association

On May 11, 2023 Protagonist Therapeutics (Nasdaq: PTGX) ("Protagonist" or "the Company") reported that additional data from the REVIVE study of rusfertide in polycythemia vera will be presented in two posters at the annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), taking place June 8-11, 2023 in Frankfurt, Germany and virtually through June 15, 2023 (Press release, Protagonist, MAY 11, 2023, View Source [SID1234631610]).

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Details are as follows:

Title: Rusfertide (PTG-300) improves polycythemia vera (PV) related symptoms in PV patients
Abstract Code: P1016
Presenting Author: Andrew Kuykendall, M.D., Assistant Member, Department of Malignant Hematology, Moffitt Cancer Center
Session Date and Time: Friday, June 9, 18:00-19:00 CEST

Title: Pharmacokinetic and pharmacodynamic effects of rusfertide in polycythemia vera: Results from an ongoing Phase 2 study in patients with elevated hematocrit values
Abstract Code: P1048
Presenting Author: Marina Kremyanskaya, M.D., Ph.D., Assistant Professor of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
Session Date and Time: Friday, June 9, 18:00-19:00 CEST

Full abstract information can be found on the EHA (Free EHA Whitepaper) 2023 Hybrid Congress website at View Source

Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-Targeting FasTCAR-T GC012F in RRMM and B-NHL and Donor-Derived CAR-T GC007g in B-ALL at EHA2023 Congress

On May 11, 2023 Gracell Biotechnologies Inc. ("Gracell" or the "Company", NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported that clinical data from three studies in B-NHL, RRMM and B-ALL will be presented at the 2023 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting taking place June 8-15 in Frankfurt, Germany, and online (Press release, Gracell Biotechnologies, MAY 11, 2023, View Source [SID1234631609]). Clinical data from GC012F, the Company’s FasTCAR-enabled autologous CAR-T cell therapy dual-targeting B-cell maturation antigen (BCMA) and CD19, in B-NHL (which was selected as an oral presentation) and RRMM, will also be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and are currently under embargo until Thursday, May 25.

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A third abstract highlights first clinical data from a Phase 1 trial evaluating GC007g, a CD19-targeted donor-derived allogeneic CAR-T cell therapy, in patients with r/r B-ALL who relapsed after receiving allogeneic stem cell transplant (allo-HSCT). The data showcases a 100% ORR and will be presented on Friday, June 9, 6:00 – 7:00 PM CEST.

"We are pleased to have our FasTCAR-T GC012F data in B-NHL selected for an oral presentation, and look forward to presenting additional data in the RRMM indication, as well as from our donor-derived CAR-T candidate for r/r B-ALL, at this year’s EHA (Free EHA Whitepaper) Congress, demonstrating the breadth of Gracell’s innovation in CAR-T cell therapy across technology platforms and indications," said Dr. Wendy Li, Gracell’s Chief Medical Officer. "The donor-derived CAR-T candidate GC007g represents a unique allogeneic approach for a group of r/r B-ALL patients that could not benefit from autologous CAR-T. We are excited to share the first data from the Phase 1 trial evaluating GC007g in this challenging set of patients and to demonstrate encouraging persistence of allogeneic CAR-T cells, durable remission, and a favorable safety profile."

CD19-Targeted Donor-Derived Allogeneic GC007g for the Treatment of r/r B-ALL

GC007g is a donor-derived CAR-T candidate that has been designed for r/r B-ALL patients who may not be eligible for autologous CAR-T therapy due to poor cell fitness, infections, and other unsuitable conditions.

Between March 2021 and May 2022, nine r/r B-ALL patients were enrolled and treated in the Phase 1 portion of the registrational Phase 1/2 clinical trial in China evaluating GC007g at two different dose levels. All patients had relapsed B-ALL following a partially or fully matched prior allo-HSCT. Six patients relapsed after haploidentical HSCT, while three patients relapsed post matched sibling donors HSCT. Three patients had received a GC007g infusion at dose level 1 (DL1) 6x105cells/kg and six patients had received an infusion at dose level 2 (DL2) 2x106cells/kg. Donor-derived CAR T-cells were successfully manufactured for all patients, with a median time from leukapheresis to infusion of 33 days (range 30-74 days).

At day 28 after infusion, 100% patients achieved minimal residual disease negative complete remission with/without incomplete count recovery (MRD- CR/CRi). At a median follow-up of 445 days (range 218-649 days), seven of nine patients remained in CR/CRi, while two patients had CD19 negative relapse. The ORR was 100% (7/7), 85.7% (6/7) and 50% (2/4) at month 3, 6, and 12, respectively. The 1-year progression-free survival (PFS) and overall survival (OS) were 76.2% and 85.7%, respectively.

Cytokine release syndrome (CRS) is presented as Grade 1 to Grade 3 events, with no Grade 4 or 5 events, and all resolved after treatment. No immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. Three patients were observed to have acute graft-versus-host disease (aGvHD) and all cases resolved after standard-of-care treatment. No chronic graft-versus-host disease (cGvHD) occurred.

The Phase 2 clinical trial of GC007g is currently recruiting patients in China.

Results will be detailed in a poster presentation, which will be available to registered attendees on the EHA (Free EHA Whitepaper) website.

Details of Gracell’s GC007g poster presentation are as follows:

Abstract title: Donor-Derived Anti-CD19 Chimeric Antigen Receptor T Cells for B-Cell Acute Lymphoblastic Leukemia: A Phase 1 Trial
Abstract code: P369
Session title: Poster session
Presentation time: Friday, June 9, 6:00 – 7:00 PM CEST
Additional Presentations for BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of B-NHL and RRMM

Gracell will also present updated results from two studies evaluating its investigational BCMA/CD19 dual-targeting FasTCAR-T GC012F candidate in B-NHL (as an oral abstract) and in RRMM (as a poster). These data are currently under embargo and will publish on Thursday, May 25, concurrently with ASCO (Free ASCO Whitepaper).

Details of the GC012F oral presentation in B-NHL are as follows:

Abstract title: Updated clinical results of first-in-human study of CD19/BCMA dual-targeting FasTCAR-T GC012F for patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma (B-NHL)
Abstract code: S234
Session title: S432 Aggressive lymphoma – CAR-T
Session location: Festhalle
Presentation time: Saturday, June 10, 4:30 – 5:45 PM CEST
Details of the GC012F poster presentation in RRMM are as follows:

Abstract title: Updated results of a multicenter first-in-human study of BCMA/CD19 dual-targeting FasTCAR-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM)
Abstract code: P869
Session title: Poster session
Presentation time: Friday, June 9, 6:00 – 7:00 PM CEST
For more information about the EHA (Free EHA Whitepaper)2023 Congress, visit www.ehaweb.org.

About GC007g

GC007g is an allogeneic CD19-targeted CAR-T cell therapy, derived from HLA-matched donors, under development for the treatment of r/r B-ALL patients who failed transplant and may not be suitable for autologous CAR-T therapy.

About GC012F

GC012F is Gracell’s FasTCAR-enabled BCMA/CD19 dual-targeting autologous CAR-T cell therapy, which aims to transform cancer treatment by driving fast, deep and durable responses with improved safety profile. GC102F is currently being evaluated in investigator-initiated trials in multiple myeloma and B-cell non-Hodgkin’s lymphoma (B-NHL), and has demonstrated a consistently strong efficacy and safety profile. In February 2023, Gracell announced regulatory clearance of Investigational New Drug applications in the U.S. and China to commence clinical trials evaluating GC012F for the treatment of relapsed/refractory multiple myeloma.

About FasTCAR

Introduced in 2017, FasTCAR is Gracell’s revolutionary next-day autologous CAR-T cell manufacturing platform. FasTCAR is designed to lead the next generation of cancer therapy and improve outcomes for patients by enhancing efficacy, reducing costs, and enabling more patients to access critical CAR-T treatment. FasTCAR drastically shortens cell production from weeks to overnight, potentially reducing patient wait times and probability for their disease to progress. Furthermore, FasTCAR T-cells appear younger and are more enhanced than traditional CAR-T cells, making them more proliferative and effective at killing cancer cells. In November 2022, FasTCAR was named the winner of the Biotech Innovation category of the 2022 Fierce Life Sciences Innovation Awards for its ability to address major industry obstacles.

About B-ALL

Acute lymphoblastic leukemia (ALL) is a type of blood cancer characterized by proliferation of immature lymphocytes in the bone marrow, which can involve either T lymphocytes (T-ALL), or B lymphocytes (B-ALL). Globally, approximately 64,000 patients are diagnosed with ALL every year with an estimated 6,540 new cases to be diagnosed in the United States in 2023.[1] B-ALL accounts for 75% of ALL diagnoses in adults.

Harpoon Therapeutics Reports First Quarter 2023 Financial Results and Provides Corporate Update

On May 11, 2023 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, reported its financial results for the first quarter ended March 31, 2023 and provided a corporate update (Press release, Harpoon Therapeutics, MAY 11, 2023, View Source [SID1234631596]).

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"Harpoon is executing its business plan in 2023 with a strengthened balance sheet, advancing multiple programs based on the TriTAC platform, and ProTriTAC IND candidates ready for further development," said Julie Eastland, President and Chief Executive Officer of Harpoon Therapeutics. "Following the $25 million preferred equity financing in March 2023, we have the financial strength to fund current operations into the second half of 2024. Additionally, we expect to see a positive impact on our cash burn over the course of the year from the restructuring implemented in the fourth quarter of last year. We also anticipate completion of enrollment for two of our Phase 1 clinical programs, HPN217 and HPN328, and achievement of key data milestones this year. Our clinical and leadership teams remain focused on advancing a rich pipeline of next-generation T cell engagers to address a broad patient population with unmet needs in both solid tumor and blood cancer indications."

Corporate Update / Recent and Upcoming Highlights

Tri-specific T cell Activating Construct (TriTAC) Platform

HPN217 (BCMA) Phase 1 trial for relapsed, refractory multiple myeloma


Interim results reported at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (cut-off of October 17, 2022) demonstrated continued evidence of clinical activity with 77% (10/13) ORR observed in the two highest target dose levels (12 and 24 mg).


Overall low incidence of cytokine release syndrome (CRS) across the patient population studied to date.


Completion of Phase 1 dose exploration is expected in the first half of 2023, with identification of a recommended Phase 2 dose(s) expected by the end of 2023.


Data presentation anticipated in the second half of 2023.

HPN328 (DLL3) Phase 1/2 trial in small cell lung cancer (SCLC) and neuroendocrine cancers


Observations in the monotherapy cohorts, as of February 2023, included early signs of anti-tumor activity, with two confirmed partial responses per RECIST in patients with SCLC.


Phase 1/2 dose and schedule optimization trial ongoing with monotherapy cohorts enrolling at the 24 mg target dose.

Enrollment in combination therapy of HPN328 with atezolizumab (Tecentriq) in patients with SCLC, as part of the Phase 1/2 dose escalation trial, is anticipated to begin in the second half of 2023.


Phase 1 dose exploration is expected to complete in the second half of 2023, including the identification of a recommended Phase 2 dose(s) in the monotherapy setting by the end of 2023.


Data presentation anticipated in the second half of 2023.

ProTriTAC

HPN601 (EpCAM)


HPN601 is Harpoon’s first conditionally active T cell engager based on the ProTriTAC platform. EpCAM is expressed in a broad range of solid tumors, potentially enabling HPN601 to address multiple indications with high unmet medical need.


IND filing timeline to enable a Phase 1 dose exploration study dependent on resource allocation.

Two additional candidates


Two new candidates for potential IND-enabling studies from the ProTriTAC platform have been identified against the targets trophoblast cell surface antigen 2 (TROP2) and Integrin-ß6 (ITGB6).

TriTAC-XR

The proprietary TriTAC-XR extended-release T cell engager platform is designed to minimize on-target CRS, a characteristic of many T cell engagers that can lead to dose limiting toxicities and can reduce the efficacy of these potent anti-tumor drugs.

AACR 2023 – Five Preclinical Posters Presented


HPN217: Poster presented on April 18, 2023:


"Anti-tumor activity of HPN217, a BCMA-targeting tri-specific T cell engager, is enhanced by y-secretase inhibitors in preclinical models"


In preclinical mouse models, y-secretase inhibitors increased the potency of HPN217 in vitro in multiple cell lines.


Combination therapy with 1mg/kg LY-3039478 and a subtherapeutic dose of 4ug/kg HPN217 led to decreased tumor burden and increased survival in a disseminated MOLP8 xenograft compared to either monotherapy alone.


HPN328: Two posters presented on April 18, 2023:

"Long-term anti-tumor immunity induced by HPN328, a DLL3-targeting tri-specific, half-life extended T cell engager, in a preclinical immunocompetent mouse model"


These results suggest that HPN328 can induce epitope spreading and prolonged anti-tumor immunity, with an increase in memory T cells, suggesting a novel mechanism for its activity and efficacy in vivo.


These findings suggest that long-term anti-tumor immunity induced by HPN328 can potentially lead to more durable anti-tumor responses in cancer patients


"Anti-tumor activity of HPN328, a DLL3-targeting tri-specific, half-life extended T cell engager, is enhanced by combining with an anti-PD-L1 antibody in an immunocompetent mouse model"


These results demonstrate the utility of combining anti-PD-L1 antibodies to enhance the anti-tumor activity of HPN328 and further supports investigation of this combination approach in patients.


Clinical studies of HPN328 in combination with atezolizumab are planned.


ProTriTAC: Two posters presented on April 17, 2023 introducing new candidates for IND-enabling studies:


"TROP2 ProTriTAC, a protease-activated T cell engager prodrug targeting TROP2 for the treatment of solid tumors"

"ITGB6 ProTriTAC, a protease-activated T cell engager prodrug targeting Integrin-ß6 for the treatment of solid tumors"

Both data sets support further investigation of Harpoon’s conditionally active next-generation T cell engager platform, ProTriTAC, with demonstrated therapeutic potential in a broad range of TROP2- and ITGB6-expressing solid tumors.

Corporate Update


$25 million preferred equity financing closed in March 2023, extending cash runway into the second half of 2024.

First Quarter 2023 Financial Results

Harpoon ended the first quarter of 2023 with $61.4 million in cash and cash equivalents compared to $53.1 million as of December 31, 2022. Following the $25.0 million preferred equity financing and year to date ATM sales, cash and cash equivalents are expected to fund current operations into the second half of 2024.


Revenue for the quarter ended March 31, 2023 was $8.6 million, compared to $5.9 million for the first quarter ended March 31, 2022. The increase in revenue was primarily due to revenue recognized in first quarter 2023 for research and development services performed on the fourth target under Harpoon’s Restated Collaboration Agreement with AbbVie, and an increase in revenue recognized related to Harpoon’s Development and Option Agreement with AbbVie for research and development services performed.


Research and development (R&D) expense for the quarter ended March 31, 2023 was $15.2 million, reduced from $20.8 million during the first quarter ended March 31, 2022. The decrease primarily arose from lower personnel-related costs due to corporate restructuring implemented in November 2022 and lower clinical and development costs due to the wind down of the HPN424 and HPN536 programs.


General and administrative (G&A) expense for the quarter ended March 31, 2023 decreased to $4.2 million, compared to $5.4 million for the first quarter ended March 31, 2022. The decrease was primarily attributable to lower personnel-related expenses, lower legal costs, and lower professional service fees to support Harpoon’s operations.


Net loss for the first quarter ended March 31, 2023 was $11.3 million, improved from $20.3 million for the first quarter ended March 31, 2022.

Evotec publishes Annual Report 2022 and Quarterly Statement for Q1 2023

On May 12, 2023 Evotec SE (Frankfurt Stock Exchange: Prime Standard, ISIN: DE0005664809; NASDAQ: EVO) reported its Annual Report for the fiscal year 2022, as well as the qualitative Quarterly Statement for the first quarter of 2023 (Press release, Evotec, MAY 11, 2023, View Source [SID1234631595]).

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Evotec’s fully audited Annual Report 2022 "Ahead of the Curve" is now available for downloading on www.evotec.com/financial-reports. Evotec had published preliminary financial results for FY2022 already on 28 March, which have remained unchanged. The publication of the final document had to be postponed after Evotec became the victim of a criminal cyber-attack that was discovered in early April.

Evotec also published a qualitative Quarterly Statement for the first quarter of 2023 today. Since the cyber-attack was discovered after the end of the first quarter, the Company’s Q1 results remain materially unaffected and saw a very strong start to the year with several deal extensions and expansions, e.g. a multi-billion-US$ extension of the Company’s neuroscience partnership with Bristol Myers Squibb, and the announcement of new partnerships, e.g. with Janssen in the field of immune-based therapies. Scale and scope of these transactions were materially larger than in the comparable period 2022.

Guidance for FY2023 remains unchanged. Evotec expects revenues in the range of € 820 – 840 m (€ 835 – 855 m at constant fx-rates) and adj. EBITDA in the range of € 115 – 130 m (€ 125 – 140 m at constant fx-rates).

Supported by the new long-term alliance with Sandoz in the field of biosimilars that was announced earlier this week, Evotec sees itself well positioned to achieve its mid-term targets of "Action Plan 2025", i.e. revenue growth to >€ 1,000 m, adjusted EBITDA of ≥€ 300 m and unpartnered research and development expenses of >€ 100 m by 2025.

In response to the criminal cyber-attack, Evotec took immediate action to contain and remediate the attack by taking its external-facing systems offline. This was deemed necessary to protect all of the Company’s partners and stakeholders. Evotec expects a fast return to full productivity, and business recovery. However, it cannot be ruled out that there could be a potential impact on the aforementioned guidance. Management will continue to monitor the situation and provide updates in subsequent reporting.

The Company will provide the next update on the financials – including an analysis of Q1 2023 developments – with the publication of the Half-Year Report 2023 that will be published on 09 August 2023.

With the publication of the audited Annual Report 2022 made today, Evotec expects to fulfil the criteria to be reinstated by Deutsche Börse/Qontigo in the relevant stock indices (MDAX, TecDAX, Prime All Share, LTecDAX, Technology All Share and CDAX). The Company anticipates the re-entry on 19 June on the grounds of the Fast Entry evaluation due on 05 June.

On 05 June 2023, Evotec will hold an ESG Capital Markets Day and present the Company’s strategic guardrails for a resilient business that remains "ahead of the curve" – even in times of global uncertainty. The ESG Capital Markets Day will be held as a virtual and invitation-only event. A recording of the broadcast will be available on www.evotec.com in the days after the event.