On January 7, 2022 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported that preliminary Monjuvi(R) U.S. net product sales for the full year of 2021 and provided financial guidance for 2022 (Press release, MorphoSys, JAN 7, 2022, View Source [SID1234598394]).

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Preliminary Monjuvi (tafasitamab-cxix) U.S. net product sales are US$ 23.6 million (€ 20.5 million) for the fourth quarter and US$ 79.1 million (€ 66.9 million) for the full year of 2021. Fourth quarter and full year 2021 results will be published on March 16, 2022.

"We are pleased that many patients have benefitted from Monjuvi since launch and we expect to see continued growth in 2022," said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. "The updated structure of our 2022 financial guidance better reflects our business model and provides greater transparency to the investment community."

Full Year 2022 Financial Guidance:

Amounts in million 2022 Financial Guidance 2022 Guidance Insights
Monjuvi U.S. Net Product Sales US$ 110m to 135m 100% of Monjuvi U.S. product sales are recorded on MorphoSys’ income statement and related profit/loss is split 50/50 between MorphoSys and Incyte.
Gross Margin for Monjuvi U.S. Net Product Sales 75% to 80% 100% of Monjuvi U.S. product cost of sales is recorded on MorphoSys’ income statement and related profit/loss is split 50/50 between MorphoSys and Incyte.
R&D expenses € 300m to 325m 2022 growth over 2021 will be driven primarily by investment in ongoing pivotal phase-3 studies, excluding transaction/restructuring/other charges related to Constellation acquisition recorded in 2021.
SG&A expenses € 155m to 170m 51% to 56% of mid-point of SG&A expenses represents Monjuvi U.S. selling costs of which 100% are recorded in MorphoSys’ income statement. Incyte reimburses MorphoSys for half of these selling expenses.
For 2022, we anticipate a year-over-year decline in SG&A, excluding transaction/restructuring/other charges related to Constellation acquisition recorded in 2021.

Additional information related to 2022 Financial Guidance:

– Tremfya royalties will continue to be recorded as revenue without any cost of sales in MorphoSys’ income statement. These royalties, however, will not contribute any cash to MorphoSys as 100% of the royalties will be passed on to Royalty Pharma.

– MorphoSys anticipates receiving royalties for Minjuvi(R) sales outside of the U.S. Guidance for these royalties is not being provided as MorphoSys does not receive any sales forecasts from its partner Incyte.

– MorphoSys does not anticipate any significant cash-accretive revenues from the achievement of milestones in 2022. Milestones for otilimab are passed on to Royalty Pharma. Milestones from all other programs remain with MorphoSys at 100%.

– MorphoSys anticipates sales of commercial and clinical supply of tafasitamab outside of the U.S. to its partner Incyte. Revenue from this supply is recorded in the "Licenses, milestones and other" category in MorphoSys’ income statement. These sales result in a zero gross profit/margin. As such, MorphoSys does not provide guidance for these sales.

– While R&D expense is anticipated to grow year-over-year due to investments in three pivotal studies, the growth is partially being offset by the consolidation of research/discovery activities.

– SG&A expense guidance range reflects savings from synergies following the acquisition of Constellation and streamlined commercialization efforts.

– Anticipated foreign exchange (USD/EUR) to impact operating expenses (R&D and SG&A) negatively by approximately 3%.

About Monjuvi(R) (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(R) 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).
In the United States, Monjuvi(R) (tafasitamab-cxix) is approved 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). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi(R) (tafasitamab) received conditional approval, 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).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Minjuvi(R) and Monjuvi(R) are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi(R) in the U.S., and marketed by Incyte under the brand name Minjuvi(R) in the EU.

XmAb(R) is a registered trademark of Xencor, Inc.

On January 7, 2022 Alexion, AstraZeneca’s Rare Disease group, reported that it has entered into an exclusive global collaboration and licence agreement with Neurimmune AG for NI006, an investigational human monoclonal antibody currently in Phase Ib development for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) (Press release, AstraZeneca, JAN 7, 2022, View Source [SID1234598393]). NI006 specifically targets misfolded transthyretin and is designed to directly address the pathology of ATTR-CM by enabling removal of amyloid fibril deposits in the heart, with the potential to treat patients with advanced ATTR-CM.

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Under the agreement, Alexion will be granted an exclusive worldwide licence to develop, manufacture and commercialise NI006.

ATTR-CM is a systemic, progressive and fatal condition that leads to progressive heart failure and high rate of fatality within four years from diagnosis.1 It remains underdiagnosed and its prevalence is thought to be underestimated due to a lack of disease awareness and the heterogeneity of symptoms.2

Marc Dunoyer, Chief Executive Officer, Alexion, said: "With 30 years of experience in developing medicines for people with rare diseases, Alexion is uniquely positioned to advance innovative science for small patient populations who are frequently underdiagnosed. We look forward to applying this expertise to the development of NI006, which is designed to clear cardiac amyloid fibril deposits with the potential to improve cardiac function for patients living with advanced ATTR-CM, who are currently underserved by existing treatment options."

There is a significant unmet medical need for patients with various types and levels of severity of amyloidosis that may require multiple mechanisms of action to address those needs. NI006, an ATTR depleter, adds a novel and complementary approach to AstraZeneca and Alexion’s pipeline of investigational therapies focused on amyloidosis and strengthens our broader commitment to addressing cardiomyopathies that can lead to heart failure.

Financial considerations
Alexion will pay Neurimmune an upfront payment of $30m with the potential for additional contingent milestone payments of up to $730m upon achievement of certain development, regulatory and commercial milestones, as well as low-to-mid teen royalties on net sales of any approved medicine resulting from the collaboration.

Neurimmune will continue to be responsible for completion of the current Phase Ib clinical trial on behalf of Alexion, and Alexion will pay certain trial costs. Alexion will be responsible for further clinical development, manufacturing and commercialisation.

The transaction is expected to close following satisfaction of customary closing conditions and regulatory clearances.

Notes

Heart failure
Heart failure (HF) is a life-threatening chronic disease that prevents the heart from pumping sufficient levels of blood around the body. HF affects approximately 64 million people worldwide. HF remains as fatal as some of the most common cancers in both men (prostate and bladder cancers) and women (breast cancer).5 Chronic HF is the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.6

AstraZeneca’s ambition is to be the leading company in HF, expanding from Forxiga today in heart failure with reduced ejection fraction (HFrEF), to the full HF spectrum including cardiomyopathies. AstraZeneca is investing in multiple investigational therapies with diverse mechanisms of action to address the spectrum of patient need in this area.

ATTR-CM
Cardiomyopathy due to ATTR is caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium. In patients with ATTR-CM, both the mutant and wild type TTR protein builds up as fibrils in tissues, including the heart. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death.

Worldwide, there are an estimated 300,000-500,000 patients with ATTR-CM3,4; however, many of those patients remain undiagnosed.

NI006
NI006 is an investigational human monoclonal antibody that specifically targets misfolded transthyretin and is designed to directly address the pathology of ATTR-CM by enabling removal of amyloid fibril deposits in the heart.

On January 6, 2022 Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported that the first patient has been dosed in a new combination arm of the ongoing multi-center, multi-dose Phase 1/2 clinical trial of BDC-1001 (Press release, Bolt Biotherapeutics, JAN 6, 2022, View Source [SID1234618690]). This arm is evaluating BDC-1001 in combination with Bristol Myers Squibb’s PD-1 checkpoint inhibitor OPDIVO (nivolumab). In parallel, Bolt continues to advance the single-agent portion of the study, following the presentation of interim dose-escalation data at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology (ESMO I-O) Congress 2021. BDC-1001 is a HER2-targeting Boltbody immune-stimulating antibody conjugate (ISAC) (trastuzumab biosimilar conjugated to a toll-like receptor 7 and 8 agonist) in development for the treatment of patients with HER2-expressing solid tumors.

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"We are excited to evaluate BDC-1001 in combination with nivolumab, a leading PD-1 checkpoint inhibitor. Pairing BDC-1001’s mechanism of action with the checkpoint inhibitor approach has the potential to yield a stronger, targeted modulation of the immune system. Initial safety and early efficacy findings reported from the ongoing monotherapy arm of the Phase 1/2 clinical trial make BDC-1001 a potentially promising candidate for the treatment of patients with HER2-expressing solid tumors," said Edith A. Perez, M.D., Chief Medical Officer of Bolt Biotherapeutics. "In the early clinical development of BDC-1001, our strategy is to follow the science, elucidating how this novel approach to engaging a patient’s immune system can eliminate tumors not addressed by currently available therapies. We look forward to investigating BDC-1001 in this first combination arm as we also continue investigation of its single-agent activity."

Bristol Myers Squibb will provide Opdivo for the combination dose escalation and combination dose expansion portions of the trial. Bolt Biotherapeutics is the study sponsor and will be responsible for costs associated with the trial execution.

About BDC-1001
BDC-1001 is a human epidermal growth factor receptor 2 (HER2) ISAC comprising a HER2-targeting biosimilar of trastuzumab conjugated with a non-cleavable linker to an innovative TLR7/8 agonist. It is currently being investigated in a Phase 1/2 clinical trial (NCT04278144) in patients with HER2-expressing solid tumors, including breast, gastroesophageal and colorectal. The trial is being conducted in four parts, and the dose-escalation monotherapy part will continue in parallel with the combination therapy study. Interim monotherapy data presented by Bolt at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology (ESMO I-O) Congress 2021 demonstrated a safe and well-tolerated profile with early clinical activity, supporting continued dose escalation and evaluation of a weekly dosing regimen.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform
ISACs are a new category of immunotherapy that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs comprise three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, with the goal of durable responses for patients with cancer.

On January 6, 2022 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, reported that Sanofi will be transitioning its rights and obligations related to SAR445136, a zinc finger nuclease gene-edited cell therapy candidate in development by Sangamo and Sanofi for the treatment of sickle cell disease (SCD), back to Sangamo over the first half of 2022 (Press release, Sangamo Therapeutics, JAN 6, 2022, View Source [SID1234607774]). The Companies are collaborating on an orderly transition, while Sangamo explores options to advance the program, including seeking a new collaboration partner. This transition follows Sanofi’s termination for convenience of the Global Research, Development and Commercialization Collaboration and License Agreement (Collaboration Agreement) between the Companies to develop genomic medicines for hemoglobinopathies. Sanofi has elected to transition the SCD program to Sangamo following a recent change in Sanofi’s cell therapy strategy.

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"Although the preliminary Phase 1/2 clinical data for the autologous sickle cell treatment are encouraging, Sanofi has made the decision to terminate the collaboration on the SAR445136 program, which is consistent with our strategy to focus on universal genomic medicine approaches," said John Reed, M.D. Ph.D., Global Head of Research and Development at Sanofi. "Sangamo has been a good partner and this decision is not a reflection on the potential of the SAR445136 program. We continue to view them as a pioneer in the area of genomic medicines and will explore other possible collaboration opportunities as we work together to transition the autologous sickle cell program back to Sangamo."

"We remain committed to progressing this program and believe SAR445136 has the potential to relieve people living with sickle cell disease of some of their most challenging symptoms. We appreciate Sanofi’s collaboration in advancing the SAR445136 program and presenting promising preliminary proof-of-concept clinical data. We expect the Phase 1/2 study to be completed as planned, for final patients in the study to be dosed in the third quarter of 2022, and for discussions regarding potential future clinical trials to continue with health authorities," said Sandy Macrae, CEO of Sangamo. "We will vigorously investigate alternative options to bring this genomic medicine forward to patients."

Sanofi notified Sangamo of its termination for convenience on December 30, 2021. Sangamo expects the Phase 1/2 PRECIZN-1 study of SAR445136 to be completed as planned. Sangamo expects that Sanofi will continue to pay the costs of the Phase 1/2 PRECIZN-1 study until the termination date of June 28, 2022, as contemplated by the Collaboration Agreement.

About the PRECIZN-1 Study

PRECIZN-1 is an ongoing first-in-human, open label, single arm, multi-site Phase 1/2 study in up to eight patients with SCD evaluating the safety and tolerability of cell therapy candidate SAR445136. The therapeutic product is manufactured by ex vivo gene editing of a patient’s own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology targeting the BCL11a gene erythroid-specific enhancer (ESE) to increase endogenous fetal hemoglobin (HbF) production. SAR445136 has received Fast Track Designation from the FDA and Orphan Medicinal Product from the EMA.

Preliminary proof-of-concept results presented at ASH (Free ASH Whitepaper) 2021 as of the cutoff date September 22, 2021 showed that no adverse events (AEs) related to investigational SAR445136 were reported through 91 weeks for the longest-treated patient and through 26 weeks for the most recently treated patient. All four treated patients experienced increases in total hemoglobin, fetal hemoglobin and percent F cells and none required blood transfusions post engraftment. Total hemoglobin stabilized by Week 26 after treatment with SAR445136 in all four patients. Most AEs reported in the screening, mobilization, apheresis and conditioning periods were SCD-related events. One serious adverse event of sickle cell anemia with crisis (vaso-occlusive crisis or VOC) was reported approximately nine months after treatment with SAR445136 in one patient, and no other SCD-related events were reported in the four patients post-infusion. The poster presentation is available on Sangamo’s website in the Investors and Media section under Events and Presentations.

On January 6, 2022 23andMe Holding Co. (Nasdaq: ME) ("23andMe"), a leading consumer genetics and research company, reported the first participant has been dosed in a Phase 1 clinical trial evaluating 23ME-00610 for the treatment of advanced solid tumors (Press release, 23andMe, JAN 6, 2022, View Source [SID1234606743]). 23ME-00610 is 23andMe’s first wholly-owned immuno-oncology (I/O) antibody to enter the clinic. The target for the new investigational antibody, CD200R1, was identified as a promising immuno-oncology target through 23andMe’s proprietary genetic and health survey database.

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"This is an important milestone for 23andMe in our mission to help people access, understand and benefit from the human genome," said Anne Wojcicki, CEO and co-founder, 23andMe. "When we started our Therapeutics group, our goal was to find new medicines validated by human genetics for people with serious unmet medical needs. That’s why we’re excited to move 23ME-00610 into the clinic to potentially help people with cancer who are in need of new treatment options."

The Phase 1 clinical trial is designed to evaluate the safety, tolerability and pharmacokinetics of 23ME-00610 in patients with locally advanced or metastatic solid tumors whose disease has progressed after standard of care treatment. 23ME-00610 is part of 23andMe’s larger drug discovery program of targets validated by human genetics across a spectrum of disease areas, including oncology, immunology, respiratory, and cardiometabolic diseases.

"Our approach to drug discovery is driven by human genetics, and we have an incredibly large database from which to select and advance genetically validated targets more efficiently, and with a potentially higher probability of success, than traditional drug discovery methods currently allow," said Kenneth Hillan, Head of Therapeutics at 23andMe. "23ME-00610 is an exciting example of how we are translating our data into investigational therapeutics."

23andMe has approximately 12 million customers, approximately 80% of whom consent to participate in research. 23andMe scientists study aggregate, de-identified genetics of these participants, alongside more than 4 billion health survey answers. Using its large database of genetically linked health traits and machine learning applied to its proprietary I/O genetic signature, 23andMe is able to pinpoint areas of the genome that contain targets for cancer therapeutics based on human genetics, including the 23ME-00610 target.

23andMe’s Immuno-oncology genetic signature
Using its genetic data, 23andMe can identify immune-related genes that are expected to have an impact on cancer biology. Specifically, germline genetics can reveal which of the immune-related genes harbor genetic variants that also alter an individual’s predisposition for developing cancer. 23andMe has developed an analytical approach, termed the immuno-oncology (I/O) genetic signature, to identify evidence for genetic variants that increase immune function while decreasing cancer risk. Using this approach, 23andMe scientists discovered that three components of the CD200R1 pathway exhibit an I/O genetic signature, including the CD200R1 receptor, the CD200 ligand, and DOK2, a mediator of downstream signaling from CD200R1. Following this genetic insight, 23andMe subsequently generated data consistent with CD200R1’s role in inhibiting anti-tumor responses in immune cells.

About CD200R1 and 23ME-00610
The CD200–CD200R1 axis is an immunological checkpoint that plays a pivotal role in maintenance of immune tolerance. CD200R1 is an inhibitory receptor expressed on T cells and myeloid cells while CD200, the ligand for CD200R1, is highly expressed on certain tumors. Binding of tumor associated CD200 to CD200R1 leads to immune suppression and decreased immune cell killing of cancer cells.

23ME-00610 is a high-affinity humanized monoclonal antibody that is designed to bind to the CD200R1 receptor and prevent the interaction of CD200 and CD200R1. Preclinical data indicate that this mechanism has the potential to reinvigorate tumor-exhausted T-cells and myeloid cells to restore their ability to kill cancer cells.

About the Phase 1 23ME-00610 Study
The first-in-human, multi-center, open-label clinical trial will determine the safety and tolerability of 23ME-00610 in people with locally advanced or metastatic solid malignancies that have progressed after standard therapy. This study will also evaluate preliminary anticancer activity, and the pharmacokinetic and pharmacodynamic profile of 23ME-00610 to identify the optimal dose and schedule for further clinical studies. After the Phase I dose escalation phase is completed, 23andMe will seek to enroll people with specific tumor types to evaluate the potential for anticancer efficacy and changes in pharmacodynamic endpoints in the expansion phase.

Participants with ECOG performance status 0-1, and with histologically diagnosed locally advanced or metastatic solid malignancy that has progressed after standard therapy for the specific tumor type are eligible. Additionally, adolescents 12 years and older with histologically diagnosed locally advanced, or metastatic solid malignancy are eligible for enrolment in the expansion phase.

R&D Day Event Information
To discuss 23ME-00610 and other developments from its Therapeutics group in more detail, the company will host a virtual R&D Day event from 8:00 a.m. to 11:30 am Pacific Time on Tuesday, January 18, 2022. The webcast event can be accessed on the day of the event at View Source A webcast replay will be available at the same address for a limited time within 24 hours after the event.