On November 9, 2021 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported it is pursuing plans to split Ligand into two separate, publicly traded companies with one featuring the OmniAb business, and the other featuring Ligand’s existing collection of core royalties and the technologies, pipeline and contracts associated with the Pelican protein expression platform and the Captisol business (Press release, Ligand, NOV 9, 2021, View Source [SID1234595035]). The spin-off is intended to create two companies with dedicated operational focus, business-specific capital allocation, agility to meet partner needs, and compelling focused investment profiles.

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"Our OmniAb business continues to have an outstanding year with the first regulatory approval for an OmniAb-derived antibody received during the third quarter and a second approval anticipated by year-end," said John Higgins, CEO of Ligand. "We believe more than ever that OmniAb offers one of the industry’s leading antibody discovery platforms and that the business is primed for success for years to come. After significant planning and analysis, we have concluded we are operating two distinct, high-growth companies within Ligand. Along with outside advisors we have determined the time is right to pursue a strategic plan to create two independent companies and accelerate investment into the OmniAb platform and technologies to further drive value."

Based on initial management and advisor review, an IPO and eventual distribution of OmniAb shares to Ligand shareholders is the leading option under consideration at this time. The IPO would be of newly issued shares of OmniAb, Inc., which would include the Ab Initio computational antigen design technology, Icagen’s ion channel technology, the xPloration high-throughput screening technology, and the suite of OmniAb transgenic animals used for antibody discovery. In an IPO, Ligand expects OmniAb to issue less than 20% of its common stock, with Ligand retaining the remaining interest, which would eventually be distributed to Ligand stockholders in a manner generally intended to qualify as a tax-free transaction. Ligand’s OmniAb strategic review is in response to the ongoing success of OmniAb, as well as the opportunity to unlock the value of this business. Ligand’s Board of Directors has not approved a specific course of action, and Ligand will continue to evaluate other options to optimize value and ensure flexibility to invest in growth. There can be no assurance that this process will result in Ligand pursuing a particular transaction or consummating any such transaction.

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation, or sale in any jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.

The latest corporate presentation can be accessed at investor.ligand.com.

Conference Call

Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time (1:30 p.m. Pacific time) to discuss third quarter financial results as well as this announcement, and to answer questions. To participate via telephone, please dial (833) 540-1167 from the U.S. or (929) 517-0358 from outside the U.S., using the conference ID 5486177. To participate via live or replay webcast, a link is available at www.ligand.com.

About OmniAb

The OmniAb discovery platform provides Ligand’s pharmaceutical industry partners access to the diverse antibody repertoires and high-throughput screening technologies to enable discovery of next-generation therapeutics. At the heart of the OmniAb platform is the Biological Intelligence of our proprietary transgenic animals, including OmniRat, OmniChicken and OmniMouse that have been genetically modified to generate antibodies with human sequences to facilitate development of human therapeutic candidates. OmniFlic (transgenic rat) and OmniClic (transgenic chicken) address industry needs for bispecific antibody applications though a common light chain approach, and OmniTaur features unique structural attributes of cow antibodies for complex targets. OmniAb animals comprise the most diverse host systems available in the industry and they are optimally leveraged through computational antigen design and immunization methods, paired with high-throughput microfluidic-based single B cell screening and deep computational analysis of next-generation sequencing datasets to identify fully human antibodies with superior performance and developability characteristics. An established core competency focused on ion channels and transporters further differentiates our technology and creates opportunities to further leverage across modalities, including antibody-drug conjugates and others. The OmniAb suite of technologies and differentiating computational capabilities and BI features are combined to offer a highly efficient and customizable end-to-end solution for the growing discovery needs of the global pharmaceutical industry.

On November 9, 2021 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease with three ongoing Phase 1 clinical trials, reported the first clinical data from its Agonist Redirected Checkpoint (ARC) platform compounds, SL-172154 and SL-279252, in patients with advanced cancer (Press release, Shattuck Labs, NOV 9, 2021, View Source [SID1234594798]).

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For SL-172154 (SIRPα-Fc-CD40L), initial monotherapy Phase 1 dose-escalation data show favorable safety and tolerability for a CD40 agonist, high levels of CD47 target occupancy and CD40 target engagement, and escalating pharmacodynamic activity in heavily pretreated, platinum resistant ovarian cancer patients. For SL-279252 (PD1-Fc-OX40L), anti-tumor activity has been observed in heavily pretreated patients, including one confirmed partial response (PR), and a second unconfirmed PR, both in patients with PD-1/L1 inhibitor pretreated non-cutaneous melanoma. Both SL-172154 and SL-279252 have been well tolerated, and a recommended Phase 2 dose has not yet been identified. These data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36th annual meeting being held Wednesday, November 10, 2021, to Sunday, November 14, 2021. Additional data from both programs will be presented at the meeting and on an investor call on November 12, 2021.

"We are incredibly pleased to provide our first clinical update for our ARC fusion proteins, SL-172154 and SL-279252, which are both in Phase 1 dose-escalation trials," said Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. "The preliminary anti-tumor activity in the first-in-human dose escalation of SL-279252 in a heavily pretreated, PD-L1 unselected patient population, is highly encouraging. In addition, the tolerable safety profile, near-complete target occupancy of CD47 and target engagement of CD40, and compelling pharmacodynamic effects observed give us confidence that SL-172154 has now emerged as a differentiated CD47 inhibitor. Our observations of target occupancy and safety data to date suggests that we will not be limited in continuing dose escalation to identify a recommended Phase 2 dose with maximal pharmacodynamic activity. We are also pleased to report that the Investigational New Drug application is now open to expand clinical development of SL-172154 into studies in AML and HR-MDS."

SL-172154 Clinical Update

As of the data cut-off of July 6, 2021, 14 heavily pretreated, platinum resistant ovarian cancer patients with a median of five prior therapies were treated with intravenous administration of SL-172154 across four dose levels on two schedules: Schedule 1 (day 1, 8, 15, 29, Q2 weeks) at 0.1, 0.3 mg/kg and Schedule 2 (weekly) at 0.3, 1.0, 3.0 mg/kg.

SL-172154 has been well tolerated at all dose levels, with no dose-limiting toxicities reported. Low grade infusion-related reactions occurred in 53% of subjects, however all subjects have completed dosing. A maximum tolerated dose (MTD) has not been reached and dose escalation continues to 10 mg/kg.

The serum concentration of SL-172154 has increased through 3 mg/kg, as target engagement on both CD47 and CD40 has approached nearly 100%. The terminal elimination phase has not yet been characterized, likely due to target-mediated drug disposition. Significant dose-dependent increases in IL-12, along with post-dose increases in multiple other serum cytokines, including CCL2, CCL3, CCL4, and CCL22, and concurrent with rapid margination of CD40+ B cells and monocytes from the peripheral blood have been observed. Initial analysis of pre- and on-treatment tumor biopsies suggests that intravenous infusion of SL-172154 induces increases in multiple immune populations within the tumor microenvironment.

Anti-tumor activity of CD47 inhibitors is dependent upon the presence of a pro-phagocytic "eat me" signal, which can be provided by tumor-targeted antibodies with FcγR binding function, chemotherapy, or radiation. Based on our current understanding of the combined profile of SL-172154, we plan to begin a combination study with liposomal doxorubicin in patients with platinum resistant ovarian cancer in the first half of 2022. In addition, an IND is now open to study SL-172154 as monotherapy and in combination with azacitidine in HR-MDS and TP53 mutant AML patients, as well as in combination with azacitidine and venetoclax in patients with AML. The combined data from these trials will inform Shattuck’s global development strategy to progress SL-172154 to become the leading CD47- and CD40-targeted cancer immunotherapy.

SL-279252 Clinical Update

As of the data cut-off of June 11, 2021, 43 patients were enrolled and dosed intravenously with SL-279252 (median age 64 years; 56% male; median of 3 [range of 0-5] prior systemic therapies for metastatic disease). 30 patients were treated on Schedule 1 (day 1, 8, 15, 29, then every two weeks) from dose level 0.0001-6 mg/kg, and 13 patients were treated on Schedule 2 (weekly) from dose level 0.3-3 mg/kg. 58% of patients were previously treated with one or more PD-1/L1 inhibitors. Both PD-L1 and OX40 expression were low in available pre-treatment tumor biopsies. SL-279252 has been well tolerated, with no treatment-related dose-limiting toxicities reported to date. An MTD has not been reached.

Serum concentrations of SL-279252 have increased with dose, and the PK profile suggests that OX40 and PD-L1 binding approached saturating concentrations at the 6 mg/kg dose level. A preliminary half-life of ~23 hours has been observed. As a point of reference, the approved dose of PD-L1 blocking antibodies is approximately 10-15 mg/kg. Dose-dependent increases in post-treatment margination of OX40+CD4+ T cells was noted through 6 mg/kg and accompanied by a trend toward increasing numbers of CD8+ memory T cells in the peripheral blood. Post-treatment biopsies suggest that treatment with SL-279252 was associated with large increases in CD8+ cytolytic T cells in the tumors of some patients.

A confirmed PR was observed in a patient with metastatic ocular melanoma who had received five prior lines of therapy, including a PD-1 inhibitor. An unconfirmed PR was observed in a patient with mucocutaneous melanoma who had received therapy with anti-CTLA-4 and anti-PD-1 inhibitors. Stable disease was observed in an additional 12 patients, including six patients who experienced stable disease for greater than 24 weeks.

Dose escalation is ongoing using Schedule 1, at 12 mg/kg.

Shattuck Webcast Investor Meeting

Shattuck will host a conference call and webcast at 8:00 a.m. ET on Friday, November 12, 2021, to discuss the clinical data from SL-172154 and SL-279252 and to provide a general corporate update. Participants are invited to listen by dialing (833) 614-1555 (domestic) or (516) 575-8754 (international) five minutes prior to the start of the call and providing the passcode 4068596. A live webcast presentation will be available here or on the company’s website at www.ShattuckLabs.com under Events & Presentations. A replay of the webcast will be archived on the company’s website following the presentation.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancers. Two Phase 1 clinical trials are ongoing, the first for patients with advanced and platinum resistant ovarian cancer (NCT04406623) and the second for patients with advanced squamous cell carcinoma of the head, neck or skin (NCT04502888).

About SL-279252

SL-279252 (PD1-Fc-OX40L) is an investigational ARC fusion protein designed to simultaneously inhibit the PD-1/PD-L1 checkpoint interaction and activate the OX40 costimulatory receptor to bolster an anti-tumor immune response receptor in patients with advanced solid tumors. A Phase 1 trial in patients with solid tumors and lymphoma is ongoing (NCT03894618).

On November 9, 2021 Exacis Biotherapeutics, Inc., a development-stage immuno-oncology company working to harness the immune system to cure cancer, reported initiation of a strategic partnership with Toronto-based Centre for Commercialization of Regenerative Medicine (CCRM) for specialty manufacturing services related to the development of Exacis’ innovative, iPSC-derived mRNA-engineered NK cell products to treat cancer (Press release, Exacis Biotherapeutics, NOV 9, 2021, View Source [SID1234594837]). The partnership also includes a cash investment into Exacis by CCRM Enterprises Holdings Ltd., the for-profit venture investment arm of CCRM, which will be used to fund operations.

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Exacis CEO Gregory Fiore, MD, commented, "We welcome CCRM as a key partner to allow us to rapidly advance our virus-free manufacturing processes to make novel NK cell products that are engineered for performance and to avoid rejection. CCRM is a recognized leader in iPSC-derived cell therapy development and manufacturing and we are thrilled to have them as a partner. Their confidence in Exacis is evidenced by the accompanying investment, by CCRM Enterprises Holdings Ltd., underscoring the unique value proposition offered by Exacis’ differentiated platform and approach to cell therapies. We look forward to partnering with CCRM’s CDMO experts to apply our mRNA based technologies to develop best-in-class products to treat challenging hematologic and solid tumors."

Cynthia Lavoie, PhD, President and CIO of CCRM Enterprises Inc. added, "We are pleased to support Exacis by way of an investment, and with our sector expertise and specialized infrastructure. This is a successful model that we have employed in the past to support promising technologies and together we will develop leading cell therapy products that utilize the substantial potential of the Exacis platform as it advances its iPSC-derived cell programs.

On November 9, 2021 Singapore-based CellVec reported that it will manufacture clinical-grade lentivirus – the first critical step in making LGR5 CAR-T cells for a first-in-human clinical trial for patients with advanced colorectal (bowel) cancer in late 2022 (Press release, Carina Biotech, NOV 9, 2021, View Source [SID1234594853]).

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Lentiviruses are widely used as a tool to deliver genes of interest to cells. In this case, the lentivirus transduces (or inserts) a group of genes to a patient’s T cells (immune cells), which turn the T cells into cancer-killing CAR-T cells targeting LGR5, a cancer stem cell marker found on colorectal cancer and other cancers.

Professor Simon Barry, Carina’s Vice President of Cell Therapy Manufacturing, said: "We are delighted to be working with CellVec because of their outstanding track record and expertise. Their flexibility and willingness to incorporate Carina’s proprietary manufacturing process was an important consideration in the selection of CellVec as our service provider."

"The partnership with Carina Biotech marks a significant milestone for us to facilitate the furtherance of gene therapies. We look forward to supporting Carina in the successful development of its LGR5 CAR-T cells," said Dr Ang Peng Tiam, Chairman of CellVec and Medical Director of Parkway Cancer Centre.

Carina’s LGR5 CAR-T cells are targeted at LGR5, a cancer stem cell marker that is highly expressed on colorectal cancer (and other cancers). Colorectal (bowel) cancer is the deadliest cancer for Australians aged 25-34 and Australia’s second deadliest cancer overall.

Young-onset colorectal cancer is often diagnosed at later stages, which have a much poorer prognosis.

Carina Biotech CEO, Dr Deborah Rathjen, said:

"We are continuing to see impressive results with our LGR5 CAR-T cell in pre-clinical testing. After our recent successful capital raise and welcoming new impact investors to our company, we are on track for a pre-IND submission in Q2 of 2022 and an IND submission to the FDA in the second half of 2022. These are important milestones towards the initiation of a Phase I/II clinical trial in patients with advanced colorectal cancer."

About LGR5
LGR5 is a cancer stem cell marker that is highly expressed on advanced colorectal cancer and some other cancers. In colorectal cancer patients, LGR5+ expression has been correlated with a particularly poor prognosis.

Cancer stem cells are a small sub-population of cells within a tumour with the ability to self-renew, differentiate into the many cell types of a tumour, initiate new tumours, and resist chemotherapy and radiotherapy (leading to relapses).

By targeting cancer stem cells, it is hoped that this therapy will reduce the tumour’s ability to generate new cancer cells, resulting in durable tumour suppression and preventing the relapses that are very common in patients with colorectal cancer.

Carina’s pre-clinical studies of the LGR5-targeted CAR-T cell have shown highly promising results with complete tumour regression and no tumour recurrence. They have also demonstrated impressive tumour access and prolonged CAR-T cell survival.

There are five approved CAR-T therapies available in the US today – all for blood cancers. One of these has been approved for use in Australia (Kymriah for the treatment of relapsed/refractory B cell acute lymphoblastic leukemia and large B cell lymphoma).

All five CAR-T therapies are generating transformational outcomes for patients with blood cancers that have failed multiple prior lines of therapy.

On November 9, 2021 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL inhibitors for severe unmet medical needs, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for bemcentinib in combination with an anti-PD-(L)1 agent as treatment for patients with STK11 altered advanced/metastatic NSCLC patients without actionable mutations (Press release, BerGenBio, NOV 9, 2021, View Source [SID1234594869]).

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Fast Track designation is intended to facilitate the development and review of drugs used to treat serious conditions and to fill an unmet medical need. It will enable BerGenBio to have more frequent interactions with the FDA throughout the drug development process so that an approved product can potentially reach the market faster.

In a separate release today 9 November 2021, BerGenBio announced that in pre-clinical NSCLC mouse models harboring STK11 mutations, sensitivity to PD-1 blockade was evaluated in the absence and presence of bemcentinib. Systemic inhibition of AXL with bemcentinib resulted in the expansion of tumor-associated T cells and restored therapeutic response to anti-PD-1 check point inhibition.

Further, data from BerGenBio’s Phase II bemcentinib and pembrolizumab combination study (BGBC008) in advanced NSCLC showed that 3 of 3 evaluable patients with identified STK11/LKB1 mutations demonstrated objective clinical response / clinical benefit to the combination of AXL inhibitor bemcentinib and pembrolizumab.

Martin Olin, Chief Executive Officer of BerGenBio, commented: "We are very pleased to receive Fast Track designation from the FDA for the second time this year and look forward to continuing to explore bemcentinib’s potential as a treatment option for NSCLC patients. It has been reported that patients habouring STK11 mutations represents up to 20% of the total NSCLC patient population, representing a large, identifiable subgroup of patients who may benefit from treatment with an AXL inhibitor such as bemcentinib."