On November 3, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported that it will present additional positive data from its Phase 1 study of MP0317 in patients with advanced solid tumors at the 2023 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held November 1–5 in San Diego, California (Press release, Molecular Partners, NOV 3, 2023, View Source [SID1234636916]). MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP).

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"MP0317 continues to demonstrate its potential to overcome the limitations of existing CD40 agonists through its unique DARPin design that allows to activate immune cells directly within the TME, while avoiding eliciting systemic toxicities," said Philippe Legenne M.D, acting CMO of Molecular Partners. "The encouraging results presented at SITC (Free SITC Whitepaper) provide clinical evidence of MP0317-induced, tumor-targeted CD40 activation. The observed remodeling of the TME and MP0317’s favorable safety profile across all dosing cohorts, including the highest planned doses, support further investigation of MP0317 in later-stage clinical studies including combination trials."

Details of the poster presenting updated results from the ongoing MP0317 Phase 1 study at the SITC (Free SITC Whitepaper) 2023 Annual Meeting can be found below. The poster will be made available on Molecular Partners’ website after the presentation.

Title: Ongoing Phase 1 study of MP0317, a FAP-CD40 DARPin, shows a favorable safety profile and early evidence of tumor-localized CD40 activation in patients with advanced solid tumors
Poster number: 721
Location & Timing: Exhibit Hall B, Friday November 3, 2023, 9am – 7pm ET

This update, based on data from 46 patients, corroborates earlier reported findings of MP0317-induced CD40 activation and related remodeling of the TME. The detection of MP0317 in tumor biopsies is associated with an increase in CD40-mediated re-programming of immune cells illustrated by IFNg production and dendritic cell (DC) maturation within the TME. Elevation of serum levels of CXCL10, an effector chemokine downstream of IFNg signaling, and changes in soluble biomarkers (sFAP & sCD40) post-MP0317 treatment support these findings. To date, one patient achieved a partial response and stable disease was observed in eight additional patients.

MP0317 continues to display a favorable safety profile across all dosing cohorts (0.03–10 mg/kg, Q3W & Q1W), with limited systemic inflammation-related adverse reactions compared to other CD40 agonists. Dose-limiting toxicity was reported in only one patient to date (transient asymptomatic Grade 3 elevation of liver enzymes), at the highest planned MP0317 dose of 10 mg/kg administered Q3W.

The positive results of this fully enrolled Phase 1 study in patients with refractory/relapsed tumors support continued clinical evaluation of MP0317 and potential investigation in combination studies. The Company expects to share final results of this study in 2024. For further information please see clinicaltrials.gov (NCT05098405).

This ongoing first-in-human Phase 1, open-label, dose-escalation study assesses the safety and tolerability as well as pharmacokinetics/pharmacodynamics and preliminary antitumor activity of MP0317 monotherapy in patients with advanced solid tumors known to express FAP and CD40 (NCT05098405). Recruitment for the dose-escalation portion of the study is complete, with 46 patients enrolled in the Netherlands and France across nine dosing cohorts. Patients received MP0317 at doses of 0.03–10 mg/kg in every-3-weeks (Q3W) or weekly (Q1W) schedules (data cut-off 10 October 2023).

About MP0317
MP0317 targets both the FAP and the immunostimulatory protein CD40 to enable tumor-localized immune activation. Through this proposed mechanism of action, MP0317 is designed to activate immune cells specifically within the tumor microenvironment, potentially delivering greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

On November 3, 2023 Omeros Corporation (Nasdaq: OMER) reported online publication of a report detailing treatment with narsoplimab of 15 adult and pediatric patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), 14 of whom had "high-risk" TA-TMA (Press release, Omeros, NOV 3, 2023, View Source [SID1234636915]). Narsoplimab is Omeros’ investigational antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system. The report was authored by an external group of investigators involved in the treatment of these patients with narsoplimab provided under Omeros’ compassionate use program.

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The report will be featured as a poster presentation at the 65th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), to be held December 9-12, 2023 in San Diego. The abstract (#3543) is available on the ASH (Free ASH Whitepaper) website at www.hematology.org or by clicking here.

The poster will be presented by Dr. Marta Castelli, Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy. Details of the presentation are as follows:

Clinical Safety and Efficacy of Narsoplimab in Pediatric and Adult Patients with Transplant-Associated Thrombotic Microangiopathy: A Real-World Experience (Abstract #3543)
Session Name: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Date: Sunday, December 10, 2023
Presentation Time: 6:00 p.m. – 8:00 p.m. PT
Location: San Diego Convention Center, Halls G-H

About Narsoplimab

Narsoplimab, also known as "OMS721," is an investigational fully human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a novel pro-inflammatory protein target and the effector enzyme of the lectin pathway of complement. Importantly, inhibition of MASP-2 has been demonstrated to leave intact the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection. A biologics license application (BLA) is pending before the U.S. FDA for use of narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), and Omeros expects to resubmit the BLA to include additional information supporting approval of narsoplimab in this indication. Narsoplimab is also in clinical development programs focused on other complement-mediated disorders, including COVID-19. FDA has granted narsoplimab breakthrough therapy and orphan drug designations for TA-TMA and orphan drug status for the prevention (inhibition) of complement-mediated thrombotic microangiopathies as well as for the treatment of TA-TMA. The European Medicines Agency has granted orphan drug designation to narsoplimab for treatment in hematopoietic stem-cell transplant.

On November 3, 2023 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of T cell engagers to selectively modulate tumor-specific T cells, reported the presentation of new positive data from its ongoing fully enrolled Phase 1 trials evaluating its lead interleukin-2 (IL-2)-based T cell engager, CUE-101, as a monotherapy and in combination with KEYTRUDA (pembrolizumab) for patients with recurrent/metastatic HPV+ head and neck squamous cell carcinoma (HNSCC) (Press release, Cue Biopharma, NOV 3, 2023, View Source [SID1234636914]). New clinical data will also be reported from the company’s ongoing Phase 1 trial evaluating its second candidate, CUE-102, for the treatment of Wilms’ Tumor 1 positive (WT1+) recurrent/metastatic cancers.

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The data will be presented in two posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 38th Anniversary Annual Meeting (SITC 2023) being held in San Diego, California and virtually November 1-5.

"I am pleased to observe the clinical benefit patients are deriving and encouraged by the positive enhancement of data from the CUE-101 clinical trials," said Christine Chung, M.D., Chair, Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, and a principal investigator participating in the clinical trial. "The notable prolongation in overall survival to over 20 months in monotherapy represents a significant advancement of clinical benefit compared to the current standard of care for this population with advanced and refractory disease. Similarly, the reported enhanced overall response rate to date in combination with pembrolizumab, compared to the historical response rate for pembrolizumab alone, is very promising for first line patients. I look forward to evaluating the trial results as they continue to mature and remain highly encouraged by the observations to date. There is a significant unmet medical need for more efficacious and less toxic treatment options for patients with recurrent/metastatic head and neck cancer, and these results from the CUE-101 trial demonstrate the potential to address this need."

Key data highlights from the fully enrolled CUE-101 combination expansion portion of the trial evaluating CUE-101 at the recommended Phase 2 dose (RP2D) of 4mg/kg plus pembrolizumab, as of data cutoff of September 27 with 17 evaluable patients, include:

DCR of 65% and ORR of 47%, demonstrating evidence of clinical activity in comparison to the 19% ORR observed with pembrolizumab treatment alone in the KEYNOTE-040 trial 1,2- This includes one complete response (CR) and seven partial responses (PR), in addition to three durable stable diseases (DSD) of ≥ 12 weeks.
56% ORR in patients with combined positive score (CPS) 1-19, in comparison to the 14% with pembrolizumab monotherapy in the KEYNOTE-040 trial 1,2, with five of the eight responses in tumors with low PD-L1 expression (CPS less than 20).
21 of the 22 patients treated with CUE-101 and pembrolizumab remain alive at time of data cutoff, including eight patients living beyond 12 months.
No unanticipated, significant safety concerns have emerged, and adverse events have been readily managed with appropriate medical care.
Key data highlights from the CUE-101 expansion portion of the Phase 1b trial evaluating CUE-101 at the RP2D as monotherapy to date with 19 evaluable patients, include:

mOS of 20.8 months in 2L+ patients (majority 3L+) treated with CUE-101 monotherapy, notably longer than the historical mOS of 7.5 and 8.4 months reported from third-party clinical trials with checkpoint inhibitors in 2L R/M HNSCC in CheckMate 1411 and KEYNOTE-040, respectively.3
DCR of 37% in late stage, refractory patients, including one confirmed PR of > 36 weeks duration and six DSD of ≥ 12 weeks. Of note, one patient has maintained stable disease (SD) for over 22 months with no detectable evidence of HPV cell-free DNA (cfDNA) in their blood after starting CUE-101 treatment and this patient recently demonstrated an unconfirmed partial response (uPR).
Key data highlights from the CUE-102 Phase 1 clinical trial to date include:

No DLTs reported to date in patients treated during the dose escalation phase at doses ranging between 1–8mg/kg of CUE-102 intravenously every 3 weeks; a MTD has not been reached.
Two patients at the 2mg/kg dose, one with gastric cancer and one with ovarian cancer have demonstrated reduction in tumor burden.
Matteo Levisetti, M.D., chief medical officer of Cue Biopharma added, "It is highly gratifying to share the positive results from the ongoing Phase 1 trial of CUE-101, highlighting its clinical activity in combination with pembrolizumab in 1L patients and the prolonged survival observed in 2L+ patients treated with CUE-101 monotherapy. The promising data further supports our confidence in defining registrational trials for CUE-101, capitalizing on the previously granted Fast Track Designation. Concurrently, the unveiling of positive findings from the ongoing CUE-102 trial have provided early evidence of tolerability and clinical activity, including reductions in tumor burden. These observations are highly encouraging, suggesting that we may have opened up a path for immunotherapy in treating multiple cancers historically resistant to check point inhibitors. The cancers overexpressing WT1 represent substantial patient populations that may benefit from CUE-102 treatment. To date, the CUE-102 trial has been enrolling patients at a rapid pace, reflecting the significant and pressing unmet medical need in these indications."

Dan Passeri, chief executive officer of Cue Biopharma, added, "The clinical data generated to date, from both our CUE-101 monotherapy and combination trials in HPV+ R/M HNSCC, as well as the early data observed in our ongoing WT1-specific CUE-102 dose escalation trial, demonstrate what we believe to be a best-in-class approach to immune modulation, and a clear path forward to realizing the full potential of activating the patient’s own immune system against cancer. We are pleased with our accomplishments to date and look forward to ongoing progress across our platform as we continue developing promising therapies for cancer patients with high, unmet medical needs."

Presentation Details
Title: A phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy in 3L and in combination with pembrolizumab in 1L recurrent/metastatic HPV16+ head and neck cancer patients
Abstract Number: 674
Presenter: Christine Chung, M.D., H. Lee Moffitt Cancer Center, Tampa, Fla. USA
Date: Saturday, November 4, 2023, Exhibit Halls A and B1, 9 a.m.–8:30 p.m. PDT

Title: A phase 1 trial of CUE-102, a novel WT1-pHLA-IL2-Fc fusion protein in HLA-A*0201 positive patients with WT1-positive recurrent/metastatic cancers
Abstract Number: 750
Presenter: Jennifer Eva Selfridge, M.D., Ph.D., University Hospitals Cleveland Medical Center, Cleveland, OH, USA
Date: Saturday, November 4, 2023, Exhibit Halls A and B1, 9 a.m.–8:30 p.m. PDT

All posters will be available to conference attendees as virtual e-posters on the virtual meeting platform November 3, 2023 at 9 a.m. PDT/12 p.m. EDT through January 12, 2024. Cue Biopharma’s posters will also be available on November 3, 2023 in the Investors & Media section of the Company’s website at www.cuebiopharma.com, under Scientific Publications and Presentations.

References:
1Harrington, K. J., et al. (Feb 2023). Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Journal of clinical oncology, DOI: View Source

2Burtness, B., et al. (Mar 2022) Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. Journal of clinical oncology, DOI: View Source

3Cohen, EW E. (Nov 2018) Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomized, open-label, phase 3 study. The Lancet, DOI: View Source(18)31999-8

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

On November 3, 2023 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing viral immunotherapies to help patients fight cancer, reported initial positive interim survival and immunological biomarker data from the ongoing randomized phase 2 clinical trial of CAN-2409 plus valacyclovir (prodrug) together with standard of care (SoC) chemoradiation followed by resection for borderline resectable pancreatic ductal adenocarcinoma (PDAC) (Press release, Candel Therapeutics, NOV 3, 2023, View Source [SID1234636913]). Data were presented today in a poster session titled ‘Neoadjuvant CAN-2409+Prodrug Plus Chemoradiation for Borderline Resectable or Locally Advanced Non-Metastatic Pancreatic Adenocarcinoma (PDAC) at the 2023 Society for Immunotherapy (SITC) (Free SITC Whitepaper) Annual Meeting.

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"Given frequent recurrence and short survival with SoC chemotherapy for non-metastatic PDAC, effective new treatment options are urgently needed," said Garrett Nichols, MD, MS, Chief Medical Officer of Candel. "We are encouraged by the improved survival associated with CAN-2409 for the treatment of borderline resectable PDAC, demonstrated for the first time in a randomized clinical trial. CAN-2409 was generally well tolerated without significant additional local or systemic toxicity when added to SoC chemoradiation."

Data Highlights as of August 21, 2023 Data Cutoff, include:

Prolonged and sustained survival was observed after experimental treatment with CAN-2409 plus prodrug in patients with borderline resectable PDAC (n=13)
An estimated survival rate of 71.4% at both 24 and 36 months, observed in patients who received CAN-2409 regimen together with SoC chemoradiation prior to surgery, versus only 16.7% survival at 24 and 36 months in patients with SoC chemoradiation prior to surgery.
Importantly, 5 out of 7 patients who received CAN-2409 were still alive at the time of data cut-off, with two patients surviving more than 45 months from enrollment. Only one patient randomized to control SoC chemotherapy remained alive at data cut-off (alive at 43 months).
Median overall survival has not yet been reached in patients who received CAN-2409; median overall survival was 12.5 months in the control arm.
Disease course was altered after salvage chemotherapy with improved CA19-9 levels and ongoing survival in CAN-2409 arm, but not in control arm.
Data showed consistent and robust activation of immune response after dosing with CAN-2409
In pancreatic tissue of patients treated with CAN-2409 plus prodrug together with SoC (but not SoC alone), dense aggregates of CD8+ granzyme B positive cytotoxic T cells, dendritic cells, and B cells were observed in the tumor microenvironment.
Increased levels of soluble granzymes B and H as well as pro-inflammatory cytokines, including IFN-γ, were observed in peripheral blood after CAN-2409 treatment, but not with control treatment.
CAN-2409 was associated with a favorable tolerability profile
Addition of CAN-2409 regimen to SoC was generally well tolerated, with no reported dose-limiting toxicities, including no cases of pancreatitis.
"The failure of immunotherapy to improve outcomes in pancreatic cancer is attributed to the highly immunosuppressive tumor microenvironment, which is largely devoid of immune cells," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "The immunological changes induced by CAN-2409, as observed in the pancreatic tissue after dosing, suggest that CAN-2409 treatment can convert the immune desert microenvironment and enable the generation of an effective antitumoral response and improve survival."

Further details from the poster will be available at time of the SITC (Free SITC Whitepaper) embargo poster presentation lift on the Candel website at: www.candeltx.com/media

About the Phase 2 Clinical Trial of CAN-2409 in Non-Metastatic Pancreatic Cancer

In its current design, the randomized, open-label phase 2 clinical trial is designed to evaluate the safety, preliminary efficacy, and biologic activity of a 2-3 injection regimen of CAN-2409 plus prodrug (valacyclovir or acyclovir) in patients with borderline resectable pancreatic cancer who are being treated with neoadjuvant chemoradiation or stereotactic body radiation therapy. After amendment in 2022, when enrollment of patients with locally advanced PDAC was discontinued, the clinical trial is exclusively focused on borderline resectable disease. In a previously completed phase 1b clinical trial, a highly significant increase in the number of CD8+ tumor infiltration lymphocytes was demonstrated at the site of the tumor after CAN-2409 treatment.

About Pancreatic Ductal Adenocarcinoma

Pancreatic cancer is a highly lethal malignancy, and is the fourth leading cause of cancer-related death in the United States among both men and women. Based on the National Cancer Institute, Surveillance, Epidemiology and End Results (SEER) database, pancreatic cancer is expected to account for 3.3% of all new cancer cases, with an estimated 64,050 new cases and estimated 50,550 deaths in 2023.1 Effective therapeutics for pancreatic cancer, including PDAC, which accounts for 90% of all pancreatic carcinomas2, are urgently needed.

Surgical resection offers the only chance of cure, thus a major therapeutic goal for subjects with non-metastatic disease is to achieve complete tumor resection. Surgical treatment (pancreaticoduodenectomy, also known as the Whipple procedure) or total or distal pancreatectomy (depending on tumor location) is generally the recommended treatment for patients diagnosed with resectable cancer; the addition of adjuvant chemotherapy has been shown to only slightly improve survival rates (20 to 23 months).2 To this end, there has been increasing use of neoadjuvant chemotherapy and chemoradiation regimens for subjects with borderline resectable pancreatic ductal adenocarcinoma. Neoadjuvant regimens are intended to debulk the tumor, thereby increasing the proportion of patients who may become eligible for surgical resection and achieve complete resection (i.e., resection with negative margins, designated ‘R0 resection’). Unfortunately, even when an R0 resection is initially achieved, cures remain elusive as most patients experience disease recurrence due to residual micrometastatic disease. In a recent meta-analysis of 20 studies representing 283 patients with borderline resectable PDAC, neoadjuvant FOLFIRINOX with or without radiotherapy, median OS was only 22.2 months (95% CI, 18.8 to 25.6 months).3

Immunotherapy with PD-1 antibodies with or without CTLA-4 antibodies has been uniformly unsuccessful in patients with PDAC due to the dense stroma that surrounds PDAC tissue and the absence of tumor infiltrating lymphocytes.

About CAN-2409

CAN-2409, Candel’s most advanced viral immunotherapy candidate, is an investigational off-the-shelf replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the disease. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. The intratumoral administration results in the release of tumor-specific neoantigens in the microenvironment. At the same time, the adenoviral serotype 5 capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This is designed to create the optimal conditions to induce an individualized and specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and ICI have previously been shown in several preclinical and clinical settings. Furthermore, more than 950 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in non-small cell lung cancer (NSCLC), borderline resectable pancreatic cancer, and localized, non-metastatic prostate cancer in ongoing clinical trials.

On November 3, 2023 Morphic Therapeutic (Nasdaq: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, reported corporate highlights and financial results for the third quarter 2023 (Press release, Morphic Therapeutic, NOV 3, 2023, View Source [SID1234636911]).

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"Morphic presented a comprehensive set of positive results from the 12-week induction phase of the EMERALD-1 study of MORF-057 in UC, showing consistent efficacy across-the-board for patients, while demonstrating no safety signals. These results are particularly impressive, given that enrollment was skewed towards the severe end of the spectrum of moderately-to-severely active UC. Notably, we continue to observe improvement in these difficult to treat patients beyond the induction phase of the study in 44-week data presented recently," commented Bruce Rogers, PhD, President of Morphic Therapeutic. "The Phase 2a study of MORF-057 clearly signaled everything we believed it would at this point in development and we are excited to continue enrolling patients in our ongoing EMERALD-2 Phase 2b study. On a separate note, what the company continues to accomplish, while Praveen is on medical leave, is a testament to the quality the team that he put in place, and we are all wishing him the very best in his continued recovery."

Third Quarter 2023 and Recent Corporate Highlights

Chief Executive Officer of Morphic Therapeutic, Praveen Tipirneni, MD, continues to improve while remaining on a medical leave of absence after suffering an emergent medical event in late September. Dr. Tipirneni is expected to return after he recovers.

In the EMERALD-1 Phase 2a trial of MORF-057 in UC, additional positive data, presented at UEGW 2023 and in a company conference call, indicate that in a moderately-to-severely-active UC population with severe disease burden, MORF-057:

•Continues to be generally well tolerated with no safety signal observed to date
•Achieved primary endpoint with high statistical significance in reduction of RHI of 6.4 points (p=0.0019)
•Showed clinical improvement consistently across key measures at week 12, including remission and response (mMCS remission of 25.7%; mMCS response of 45.7%)
•Demonstrated RHI change ≥7 points in 48.6% of patients and RHI remission in 22.9% of patients
•Led to clinical improvement in mMCS within the 12-week induction period for 76% of patients, including advanced therapy-experienced patients
•PK/PD results confirm those seen in healthy volunteer studies
◦Median RO >99% and sustained saturation at week 12
◦Predicted lymphocyte subset changes observed, consistent with engagement of α4β7
•Demonstrated deepening of clinical effect beyond the 12-week induction period, with symptomatic remission rates continuing to increase out to 44 weeks in both advanced treatment-naïve and advanced treatment-experienced patients

Ongoing MORF-057 EMERALD Phase 2 Development Program Updates

•Continued the 40-week maintenance phase of the EMERALD-1 study as planned
•EMERALD-2 global Phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 in patients with moderate-to-severe UC continues to enroll as projected
▪The primary endpoint of EMERALD-2 is the clinical remission rate as measured by mMCS at 12 weeks and is expected to report in the first half of 2025
•The Phase 2b study of MORF-057 in Crohn’s Disease is anticipated to begin in the first half of 2024

MORF-057 Preclinical Studies

•Presented preclinical data on rational selection of combination therapy for inflammatory bowel disease (IBD) treatment using an established clinical mode at UEGW 2023
◦This study explored preclinical combination models in UC and preliminarily examined the potential utility and rationale of combining anti-inflammatory mechanisms with α4β7 integrin inhibition in IBD

Pipeline Programs
•Continued late-stage preclinical work in the MORF-088 small molecule αvβ8 inhibitor program, with initiation of clinical trials anticipated in the first half of 2024
◦αvβ8 inhibition holds promise as a novel mechanism to treat myelofibrosis, a rare blood cancer, because the αvβ8 integrin is an activator of TGF-β which is believed to play a central role in the pathogenesis of myelofibrosis

Financial Results for the Third Quarter 2023

•Net loss for the quarter ended September 30, 2023, was $36.2 million or $0.73 per share compared to net income of $30.0 million or $0.78 per share for the same quarter last year
•Revenue was $0 million for the quarter ended September 30, 2023, compared to $2.1 million for the same quarter last year due to the conclusion of the Company’s research and development collaborations with AbbVie and Janssen
•Research and development expenses were $34.4 million for the quarter ended September 30, 2023, as compared to $25.2 million for the same quarter last year. The increase was primarily attributable to higher manufacturing and development costs along with higher pre-clinical and phase 2 clinical trial costs to support our lead product candidate, MORF-057
•General and administrative expenses were $10.4 million for the quarter ended September 30, 2023, compared to $8.3 million for the same quarter last year. The increase was due to increased non-cash stock-based compensation expenses and higher payroll costs

As of September 30, 2023, Morphic had cash, cash equivalents and marketable securities of $725.1 million, compared to $731.4 million as of June 30, 2023. Based on its current operating plan, Morphic believes its existing cash, cash equivalents and marketable securities as of September 30, 2023, will be sufficient to fund operating expenses and capital expenditure requirements into the second half of 2027.

About MORF-057

Morphic is developing MORF-057 as a selective, oral small molecule inhibitor of the α4β7 integrin for patients with inflammatory bowel disease (IBD). α4β7 has been clinically validated as a target for the treatment of IBD by the success of the approved injectable antibody therapeutic vedolizumab. MORF-057, like vedolizumab, is designed to block the interactions between α4β7 on the surface of lymphocytes and the mucosal endothelial cell ligand MAdCAM-1, substantially reducing lymphocyte migration from the bloodstream into intestinal mucosal tissues and avoiding inflammation that is associated with IBD.

About the EMERALD-1 Study

EMERALD-1 (MORF-057-201) is an open-label multi-center phase 2a trial designed to evaluate the efficacy, safety, and tolerability of MORF-057 in adults with moderate to severe ulcerative colitis. The 35 patients enrolled in the main cohort of the EMERALD-1 study have been treated with 100 mg BID (twice daily) at sites in the United States and Poland. The primary endpoint of the trial was the change in Robarts Histopathology Index (RHI), a validated instrument that measures histological disease activity in ulcerative colitis at 12 weeks compared to baseline. Patients will continue for an additional 40 weeks of maintenance therapy followed by a 52-week assessment. Secondary and additional pre-specified measures in the EMERALD-1 study include change in the modified Mayo clinic score, safety, pharmacokinetic parameters and key pharmacodynamic measures including α4β7 receptor occupancy and lymphocyte subset trafficking.

About the EMERALD-2 Study

EMERALD-2 (MORF-057-202) is a global phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 that is currently enrolling patients with moderate-to-severe ulcerative colitis. The primary endpoint of EMERALD-2 is clinical remission rate as measured by the Modified Mayo Clinic Score (mMCS) at 12 weeks. EMERALD-2 will also measure several secondary and exploratory endpoints based on the mMCS as well as histologic, pharmacokinetic and pharmacodynamic measures, and safety parameters. Patients in the EMERALD-2 study will be randomized to receive either 200 mg BID MORF-057, 100 mg BID MORF-057, a QD (once daily) dose of MORF-057, or a placebo dose. Following the 12-week induction phase, all patients will receive MORF-057 for 40-weeks of maintenance dosing. For more information about the EMERALD clinical trials of MORF-057, please click here.