On June 20, 2024 Yellowstone Biosciences ("Yellowstone" or "the Company"), a pioneer of soluble bispecific T-cell receptor (TCR)-based therapies for human leukocyte antigen (HLA) Class II (HLA-II) targets in oncology, reported to unlock a new class of therapeutically targetable, frequently expressed antigens with potential to significantly transform patient lives (Press release, Yellowstone Bioscience, JUN 20, 2024, View Source [SID1234644469]). Syncona Limited ("Syncona") committed £16.5 million to fund the Company in progressing its operational build, lead programme in acute myeloid leukaemia (AML), and exploration into expanding its pipeline.

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Spun out of the University of Oxford with the support of Oxford University Innovation (OUI), Yellowstone is built around the pioneering research of Professor Paresh Vyas, a world-renowned scientific academic, key opinion leader and practising clinician with a specialist focus on AML. Over 20 years, Prof. Vyas’ laboratory has collected a proprietary biobank of over 10,000 samples from over 3,000 AML patients, including a rare cohort of patients cured by allogeneic blood cell transplantation. From this cohort a novel set of frequently expressed peptide antigens presented by HLA Class II were identified, which could unlock a new class of highly selective cancer therapeutics.

With privileged access to this biobank, Yellowstone has been formed to develop soluble bispecific TCR-based therapeutics targeting HLA Class II presented peptides on the surface of cancer cells in a number of cancers with high unmet need. By targeting peptides presented by HLA-II molecules, the Company’s bispecific T-cell engagers have the potential to selectively kill target tumour cells, whilst sparing healthy cells. The Company will focus initially on its lead programme in AML, which accounts for 62% of all leukaemia deaths1 and where there is no universally agreed standard of care for the majority of patients. Beyond AML, Yellowstone’s technology also has the potential to extend life and change the treatment landscape in other common solid tumours that express HLA-II, including ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, prostate cancer, breast cancer, renal cancer and melanoma.

Yellowstone will be led by a world-class management team, including Prof. Vyas, as Co-founder and Chief Scientific Officer, and Julian Hirst, who joins as Co-founder and Chief Financial Officer, bringing with him 20 years’ experience in biotechnology and investment banking, including senior finance roles at Immunocore and MiroBio. Neil Johnston also joins as Executive Chair, having spent 17 years at Novartis, most recently as Global Head of Business Development and Licensing. The Company will be guided by Syncona, a leading FTSE 250 life sciences investor, who has supported company launch and will continue to shape Yellowstone’s operational build. Chris Hollowood, CEO of Syncona, and Gonzalo Garcia, Investment Partner at Syncona, will hold Board positions at Yellowstone as part of the lead investor’s ongoing involvement.

Professor Paresh Vyas, Co-founder and Chief Scientific Officer of Yellowstone, said: "Frequently expressed antigens that can be targeted therapeutically are notoriously difficult to find but, through two decades of research, we have identified a new class of targets that have potential to treat cancer and extend patient’s lives. We believe that our technology has the potential to selectively kill tumour cells, whilst sparing healthy cells, in a range of cancers. The strategy that we have built, alongside Syncona, will initially focus on developing highly selective TCR-based therapies for AML, where we have formidable experience and data. Beyond that, we are committed to broadening our pipeline to other cancer settings to maximise Yellowstone’s potential."

Gonzalo Garcia, Investment Partner at Syncona and Non-executive Director at Yellowstone, commented: "Yellowstone is the latest company formed from Syncona’s model of creating and building businesses based on exceptional science and world-class founders. The work Prof. Vyas has undertaken in this field is truly remarkable. Although difficult to identify, tumour-selective, frequently expressed antigens are particularly strong cancer targets as they allow development and manufacturing of therapies that can treat large numbers of patients. We believe that Syncona can build a globally leading UK company around this novel discovery that has significant patient and commercial potential."

Yellowstone’s academic founders received support during the spin out from OUI’s Dr. Susan Campbell and Dr. Benedicte Menn. As part of their ongoing involvement, OUI will hold a board observer position at the company.

Dr Benedicte Menn, Senior Investment Manager, Oxford University Innovation, said: "With ambition to become a world class UK company, Yellowstone is our latest spinout from the University of Oxford. The company has potential to treat and extend the life of patients with different forms of cancer, starting with acute myeloid leukaemia. We’re delighted that Yellowstone and Syncona are partnering on this launch and look forward to tracking the progress of the pipeline."

On June 20, 2024 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported that the company has entered into a delisting agreement with Novartis BidCo AG and Novartis AG following the successful closing of the acquisition of MorphoSys by Novartis in May 2024 (Press release, MorphoSys, JUN 20, 2024, View Source [SID1234644468]). Novartis BidCo Germany AG (together with Novartis BidCo AG and Novartis AG hereinafter collectively referred to as "Novartis") also informed MorphoSys of their intention to merge MorphoSys into Novartis by initiating a squeeze-out of MorphoSys’ minority shareholders.

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In April 2024, Novartis submitted a voluntary public takeover offer for all outstanding MorphoSys no-par value bearer shares, offering MorphoSys shareholders € 68.00 per share in cash (the "Takeover Offer"). The acceptance period of the Takeover Offer and the statutory two-week additional acceptance period ended on May 13, 2024, and May 30, 2024, respectively. As of June 20, 2024, Novartis holds approximately 91.04% of the total MorphoSys share capital, including purchases by Novartis outside of the Takeover Offer. As a result, Novartis is the majority shareholder of MorphoSys, making MorphoSys a Novartis company.

MorphoSys and Novartis Sign Delisting Agreement

Following the settlement of the Takeover Offer, MorphoSys and Novartis today signed an agreement confirming that Novartis intends to launch a public delisting purchase offer (the "Delisting Offer") for all outstanding MorphoSys no-par value bearer shares that are not presently held by Novartis. Novartis will offer MorphoSys shareholders € 68.00 per share in cash, corresponding to its preceding Takeover Offer.

The Delisting Offer document is expected to be published by Novartis in early July 2024 after the German Federal Financial Supervisory Authority ("BaFin") has approved its publication, in accordance with the provisions of the German Securities Acquisition and Takeover Act. Once the Delisting Offer document is published by Novartis, a four-week (but not less than 20 U.S. business days) offer period for MorphoSys shareholders to tender their shares will commence.

Following publication of the Delisting Offer document, the MorphoSys Management Board and Supervisory Board will issue a joint reasoned statement in accordance with sec. 27 of the German Securities Acquisition and Takeover Act. Additionally, in accordance with U.S. securities laws, Novartis will file the Delisting Offer document and a Tender Offer Statement on Schedule TO, and MorphoSys will file the joint reasoned statement and a Solicitation/Recommendation Statement on Schedule 14D-9 with the U.S. Securities and Exchange Commission (the "SEC").

Following BaFin approval, the Delisting Offer document and additional information relating to the Delisting Offer will be published by Novartis on this website: View Source The Tender Offer Statement on Schedule TO and the Solicitation/Recommendation Statement on Schedule 14D-9 will be made available on the SEC’s website at www.sec.gov and under the "SEC Filings" section of the MorphoSys website at www.morphosys.com/en/investors.

Following the publication of the Delisting Offer document by Novartis, MorphoSys will apply for revocation of the admission to trading of MorphoSys shares on the regulated market of the Frankfurt Stock Exchange. MorphoSys also intends to delist from NASDAQ. After the delisting becomes effective, MorphoSys shares will no longer be traded on the regulated market of the Frankfurt Stock Exchange or on NASDAQ, and follow-up obligations from such a public listing no longer apply. Additionally, following deregistration with the SEC, MorphoSys will no longer be required to file reports with the SEC. Both the delisting from the Frankfurt Stock Exchange and the delisting from NASDAQ are expected to take place in the third quarter of 2024.

MorphoSys and Novartis Intend to Implement a Merger Squeeze-out of MorphoSys’ Minority Shareholders

Novartis also informed MorphoSys of their intention to merge MorphoSys into Novartis. In this context, Novartis has proposed entering negotiations with the MorphoSys Management Board regarding a merger agreement.

Given Novartis holds approximately 91.04% of the total MorphoSys share capital, Novartis is able to facilitate a squeeze-out of MorphoSys’ minority shareholders in connection with such a merger. Novartis will therefore seek the transfer of MorphoSys’ minority shareholders’ shares to Novartis against an adequate cash compensation (merger squeeze-out). The amount of the cash compensation has not yet been determined.

It is planned that the necessary shareholders’ resolution on the merger squeeze-out will be adopted at the MorphoSys Annual General Meeting expected to take place in August 2024.

On June 20, 2024 Tubulis reported that the first patient has been treated in its first Phase I/IIa trial (NAPISTAR 1-01, NCT06303505) (Press release, Tubulis, JUN 20, 2024, View Source [SID1234644467]). The study is evaluating Tubulis’ next-generation antibody-drug conjugate (ADC) TUB-040 in patients with platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC), who have exhausted other available treatment options. TUB-040 targets NaPi2b, a highly overexpressed antigen in ovarian cancer and lung adenocarcinoma. The candidate is the first to enter the clinic from the company’s growing pipeline and represents one of Tubulis’ two lead candidates developed using its proprietary suite of platform technologies, which enable the creation of uniquely matched ADCs with superior biophysical properties.

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The multicenter, first-in-human, dose escalation and optimization Phase I/IIa study aims to investigate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy. The trial will be conducted in the US as well as the UK, Spain, Belgium, and Germany. Phase Ia comprises the dose escalation and will determine safety and the maximum tolerated dose or the identified dose for optimization, whereas Phase IIa will focus on dose optimization, safety, and preliminary efficacy of TUB-040. The first patient has been dosed in the US following IND approval by the FDA.

"ADCs are beginning to show their potential as a core treatment modality replacing conventional chemotherapy for several solid tumor indications. Based on our preclinical data we are convinced that TUB-040 can represent a new option for the effective treatment of NSCLC and ovarian cancer patients," said Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis. "The novel P5 technology we use in TUB-040 improves upon current limitations due to off-target toxicity and restricted durability, the main challenges of current ADC treatments. By achieving reduced non-target toxicity together with a more specific, more powerful, and continued on-tumor delivery of the payload, we aim to improve long-term anti-tumor responses and, ultimately, clinical outcomes for patients."

"Initiating our first clinical trial represents an important milestone for the entire Tubulis team and underscores our vision to innovate on all fronts of the ADC design for patient benefit," said Dominik Schumacher, PhD, Chief Executive Officer and Co-founder of Tubulis. "Our objective is to achieve clinical proof-of-concept for our lead candidate, TUB-040, and validate our differentiated platform approach to ADC development."

TUB-040 consists of a humanized, target-specific, Fc-silenced IgG1 antibody equipped with Tubulis’ proprietary Tubutecan linker-payload technology, which is based on P5 conjugation chemistry and the topoisomerase-1 inhibitor Exatecan. Tubulis recently presented a comprehensive preclinical data set at AACR (Free AACR Whitepaper), demonstrating the superior stability and minimal loss of linker-payload conjugation for their lead candidate. In a range of preclinical models, Tubulis was also able to show high and long-lasting anti-tumor responses, even at lower expression levels of NaPi2b, with an excellent safety and tolerability profile.

About TUB-040 and the P5 Technology

Tubulis’ lead antibody-drug conjugate (ADC) TUB-040 is directed against Napi2b, an antigen highly overexpressed in ovarian cancer and lung adenocarcinoma. It consists of an IgG1 antibody targeting Napi2b connected to the Topoisomerase I inhibitor Exatecan through a cleavable linker system based on the company’s proprietary P5 conjugation technology with a homogeneous DAR of 8. P5 conjugation is a novel chemistry for cysteine-selective conjugation that enables ADC generation with unprecedented linker stability and biophysical properties. It originated from the fundamental work of Prof. Christian Hackenberger at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), which unlocked the use of phosphorus chemistry for superior bioconjugation. Preclinical pharmacokinetic analysis also demonstrated that TUB-040 efficiently delivers its payload to the tumor while reducing off-site toxicities. The candidate is currently being investigated in a multicenter Phase I/IIa study (NAPISTAR 1-01, NCT06303505) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy.

On June 20, 2024 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on the treatment of cancer and autoimmune diseases, reported that China National Medical Products Administration (NMPA) has accepted and granted priority review to a biologics license application (BLA) for tafasitamab in combination with lenalidomide for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT) (Press release, InnoCare Pharma, JUN 20, 2024, View Source [SID1234644466]).

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Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare, said, "Today’s BLA acceptance marks an important milestone for InnoCare. DLBCL is the most common type of non-Hodgkin lymphoma globally, and there is a significant unmet need for DLBCL patients in China. We believe that tafasitamab regimen will bring a novel treatment therapy to DLBCL patients in China."

Tafasitamab, a humanized Fc-modified cytolytic CD19-targeting immunotherapy, in combination with lenalidomide has already been approved for the treatment of eligible DLBCL patients in Hong Kong. Furthermore, under the early access program in the Bo’ao Lecheng International Medical Tourism Pilot Zone and the Guangdong-Hong Kong-Macao Greater Bay Area, prescriptions of tafasitamab in combination with lenalidomide were issued at the Ruijin Hainan Hospital and Guangdong Clifford Hospital for eligible DLBCL patients.

Tafasitamab is approved under accelerated approval by the U.S. Food and Drug Administration (FDA), and conditional approved by the European Medicines Agency (EMA), in combination with lenalidomide for the treatment of relapsed or refractory DLBCL adult patients who are not eligible for ASCT.

DLBCL is the most common type of non-Hodgkin lymphoma (NHL), and its incidence accounts for 31% to 34% of NHL globally. In China, DLBCL accounts for 45.8% of all NHLs1.

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

MorphoSys and Incyte entered into: (a) in January 2020, a collaboration and licensing agreement to develop and commercialize tafasitamab globally; and (b) in February 2024, an agreement whereby Incyte obtained exclusive rights to develop and commercialize tafasitamab globally.

In August 2021, Incyte entered into a collaboration and license agreement with InnoCare for the development and exclusive commercialization of tafasitamab in hematology and oncology in Greater China.

In the United States, Monjuvi (tafasitamab-cxix) received accelerated approval by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). In Europe, Minjuvi (tafasitamab) received conditional Marketing Authorization from the European Medicines Agency in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

XmAb is a registered trademark of Xencor, Inc.

Monjuvi, Minjuvi, the Minjuvi and Monjuvi logos and the "triangle" design are registered trademarks of Incyte.

On June 20, 2024 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," reported the presentation of preclinical data from the Company’s highly differentiated mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) program at the 4th American Association for Cancer Research (AACR) (Free AACR Whitepaper) International Meeting: Advances in Malignant Lymphoma (Press release, HotSpot Therapeutics, JUN 20, 2024, View Source [SID1234644465]).

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MALT1 is a component of the CARD11-BCL10-MALT1 (CBM) protein complex, which serves as a key regulator of NF-kB signaling in cells, including B and T cells. MALT1 is implicated in a range of hematological malignancies, including Non-Hodgkin’s lymphoma, as well as other lymphomas and selected solid tumors. Leveraging the Company’s proprietary Smart AllosteryTM platform, HotSpot has developed a potential first-in-class small molecule designed to selectively inhibit the scaffolding function of MALT1, a dominant driver of the NF-kB pathway, while sparing MALT1’s protease function.

"Given the NF-kB pathway’s role as an oncogenic driver in a range of hematological and solid tumors, the scaffolding function of MALT1, a key activator of the pathway, represents an attractive therapeutic target," said Geraldine Harriman, Co-Founder and Chief Scientific Officer of HotSpot. "At HotSpot, we’ve utilized our Smart AllosteryTM platform to develop HST-1021, a potentially first-in-class MALT1 scaffolding inhibitor. These preclinical data support the highly differentiated profile of HST-1021, demonstrating its broad and potent inhibitory activity with no observed adverse effects on T cells."

The presentation describes preclinical data for HST-1021, HotSpot’s MALT1 scaffolding inhibitor development candidate:

HST-1021 demonstrated potent inhibition of NF-kB and AP1 activity in vitro, two key markers of MALT1 scaffolding activity.
In contrast to MALT1 protease inhibitors, HST-1021 had no observed effect on MALT1 protease activity or T-cell function, and HST-1021 did not deplete Treg cells in vivo. HotSpot believes this supports the potential for mitigation of the risk of autoimmune disease resulting from chronic MALT1 protease function inhibition and could allow for broad combination use.
HST-1021 demonstrated more significant and broader anti-tumor activity as compared to a MALT1 protease inhibitor.