On January 7, 2022 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported its strategic priorities and anticipated milestones for 2022 (Press release, Mersana Therapeutics, JAN 7, 2022, View Source [SID1234598401]). Anna Protopapas, President and CEO of Mersana Therapeutics, Inc. will provide a business update at the upcoming virtual 40th Annual J.P. Morgan Healthcare Conference on Wednesday, January 12, 2022.

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"During 2021, we have made substantial progress in executing on the four strategic pillars that underlie our vision of building Mersana into an ADC leader: building UpRi into a foundational medicine in ovarian cancer, advancing a diverse pipeline of first-in-class ADCs addressing areas of high unmet medical need, driving ADC innovation and building Mersana into an organization with world-class talent," said Anna Protopapas. "With UPLIFT and UPGRADE ongoing and UP-NEXT expected to initiate in Q2 2022, we have established a highly differentiated development strategy with the goal of bringing UpRi to a broad population of ovarian cancer patients with limited options. With XMT-1660 and XMT-2056, two first-in-class candidates initiating Phase I dose escalation in mid-2022 and two additional candidates that will be disclosed during the course of year, we are expanding and diversifying our pipeline by leveraging our three innovative product engines: Dolasynthen, Dolaflexin, and Immunosynthen."

Ms. Protopapas continued: "Our selection as a Top Place to Work by the Boston Globe is validation of the talent we have attracted to Mersana and the mission-focused culture we have built."

Corporate Updates and 2022 Anticipated Goals and Milestones

Build Upifitamab Rilsodotin (UpRi), a first-in-class Dolaflexin ADC targeting NaPi2b, as a foundational medicine in ovarian cancer:

UPLIFT, a single-arm registrational trial in platinum-resistant ovarian cancer, is expected to complete enrollment in the third quarter of 2022. UPLIFT is enrolling a broader population of patients with platinum-resistant ovarian cancer than other studies in this space through more flexible inclusion criteria with respect to lines of therapy, prior therapies, and underlying comorbidities. The primary endpoint is based on objective response rate in NaPi2b high patients, which represent approximately two-thirds of the patients as determined by a robust diagnostic assay, with a secondary endpoint in the overall population. The Company plans to enroll approximately 100 patients with high NaPi2b expression and up to 180 patients overall.

UP-NEXT, a Phase 3 monotherapy maintenance trial in platinum-sensitive recurrent ovarian cancer, is expected to initiate in the second quarter of 2022. The design of UP-NEXT was informed by discussions with the FDA and CHMP and could serve as a confirmatory trial that expands UpRi into earlier lines of therapy. UP-NEXT will enroll platinum-sensitive patients who have achieved a response or stable disease after platinum therapy. Prior PARP therapy is required only for BRCA mutant patients. NaPi2b high patients, which represent approximately two-thirds of the ovarian cancer population, will be enrolled. In recognition of the unmet medical need and the lack of a standard of care for these patients, the trial will be randomized against placebo.

UPGRADE, a Phase 1/2 combination umbrella trial in platinum-sensitive ovarian cancer, continues to enroll with interim data expected in the second half of 2022. UPGRADE is currently in a Phase 1 dose escalation trial evaluating the combination of carboplatin with UpRi for up to six cycles followed by UpRi continuation as a single-agent. The dose escalation portion of the trial is intended to determine the recommended Phase 2 dose in combination with carboplatin. The expansion portion of the trial is intended to provide proof of concept for a potential new standard of care for platinum-sensitive ovarian cancer earlier in the disease by demonstrating that the combination of platinum and UpRi followed by UpRi continuation as a single-agent could result in improved efficacy and tolerability with the ultimate goal of improved clinical benefit for patients. The trial will inform further development of UpRi in this broader and earlier line patient population.
Build out a pipeline of highly impactful cancer medicines:

XMT-1592, a first Dolasynthen ADC targeting NaPi2b, is currently in a Phase 1 trial, with dose exploration expected to be complete in the second half of 2022. XMT-1592 was designed to provide Mersana with a second shot on goal in NSCLC adenocarcinoma based on the increased preclinical activity shown in this indication. The Company is continuing dose exploration to determine the recommended Phase 2 dose and plans to provide an update on next steps for this program in the second half of 2022.

XMT-1660, a first-in-class Dolasynthen ADC targeting B7-H4, is expected to initiate a Phase 1 dose escalation trial in mid-2022. XMT-1660 targets B7-H4, a target selectively expressed on tumors in areas of high unmet medical need including breast, endometrial and ovarian cancers. XMT-1660 is a Dolasynthen ADC that utilizes the Company’s unique DolaLock payload with controlled bystander effect. Clinical experience to date with ADCs carrying the DolaLock payload has demonstrated no association with severe neutropenia, peripheral neuropathy or ocular toxicity.

XMT-2056, a first-in-class HER2-targeted Immunosynthen STING-agonist ADC, is expected to initiate a Phase 1 dose escalation trial in mid-2022. XMT-2056 is the Company’s first ADC candidate developed using Immunosynthen, its novel STING-agonist immunostimulatory ADC platform. XMT-2056 is designed to offer a differentiated and complementary therapeutic approach to the treatment of HER2-expressing tumors. XMT-2056 targets a novel HER2 epitope with differentiated binding from trastuzumab and pertuzumab, providing an opportunity for development as a single-agent as well as in combination with well-established and investigational anti-HER2 agents. Across multiple preclinical models, XMT-2056 monotherapy demonstrated increased efficacy in comparison to benchmark agents such as a trastuzumab-TLR7/8 agonist ADC as well as a small molecule systemically-administered STING agonist. XMT-2056 also demonstrated efficacy in both high and low HER2 expression models. In addition, in preclinical models, XMT-2056 showed increased efficacy in combination with trastuzumab. XMT-2056 was generally well-tolerated in non-human primate studies with no clinical signs and no adverse findings in clinical pathology or histopathology after single and repeat IV doses.
Build innovation and scientific leadership in ADCs

The Company plans to disclose two new development candidates, XMT-2068 and XMT-2175, during the first half of 2022. Both candidates were created utilizing the Company’s Immunosynthen platform and are STING-agonist ADCs targeting tumor-associated antigens in the tumor microenvironment with broad expression across indications.
Upcoming Events

The Company will review these corporate updates and milestones during its upcoming presentation at the upcoming virtual 40th Annual J.P. Morgan Healthcare Conference on Wednesday, January 12, 2022 at 3:00 pm ET.

On January 6, 2022 Tiziana Life Sciences (Nasdaq: TLSA) ("Tiziana"), a biotechnology company enabling breakthrough immunotherapies via novel routes of drug delivery, reported that senior management will present at the Biotech Showcase Conference and be available for one-on-one meetings throughout the conference (Press release, Tiziana Life Sciences, JAN 6, 2022, View Source [SID1234598400]). The conference is being held virtually from January 10th -12th and also during January 17th -19th.

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Conference details can be found below:

Biotech Showcase

Date: January 10-12 and 17-19, 2022
Format: On-demand presentation (available January 7, 2022) and one-on-meetings
Registration: Click here

On January 7, 2022 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that Søren Bregenholt, Chief Executive Officer, will participate and host one-on-one investor meetings at the following upcoming investor conferences (Press release, Alligator Bioscience, JAN 7, 2022, View Source [SID1234598399]):

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H.C. Wainwright BioConnect Conference, US
Location: Virtual Event

Date: January 10-13

The presentation will be available online – January 10-13, 2022.

Please visit the conference linkto register and view the event.

Redeye Fight Cancer Seminar – Outlook 2022
Location: Virtual Event
Date: Thursday, January 20, 2022
Time: 9:00 – 16:00, company presentation schedule will be updated by Redeye closer to the event and will be live broadcasted at Fight Cancer Seminar – Outlook 2022 | Redeye for Redeye members.

All presentations will be available via a digital library, which is accessible to event participants only. Please contact the organizers to if you wish to attend or Julie Silber if you wish to schedule a meeting with Alligator.

On January 7, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a biotechnology company creating precisely targeted therapies for clinically proven kinase targets in cancer, reported that the first patient has been dosed in ARROS-1, its Phase 1/2 clinical trial evaluating NVL-520 in patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) and other advanced solid tumors (Press release, Nuvalent, JAN 7, 2022, https://www.nuvalent.com/nuvalent-announces-first-patient-dosed-in-arros-1-phase-1-2-clinical-trial-of-nvl-520-its-novel-ros1-selective-inhibitor/ [SID1234598395]). NVL-520, Nuvalent’s lead product candidate, is a novel ROS1-selective inhibitor designed to address the clinical challenges of emergent treatment resistance, CNS adverse events, and brain metastases that may limit the use of currently available ROS1 kinase inhibitors.

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"The initiation of patient dosing with NVL-520 in ARROS-1 is a significant milestone for Nuvalent as we transition from a preclinical to clinical stage company," said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. "We designed NVL-520 with the goal of fulfilling a specific target product profile developed in collaboration with leading physician-scientists who are actively treating patients with ROS1-driven cancers today. We are encouraged by the preclinical data generated to date, which provide evidence that NVL-520 represents a differentiated ROS1-selective inhibitor with the potential to overcome the limitations of current tyrosine kinase inhibitor therapies and provide a new therapeutic option for patients in need."

ARROS-1 is a Phase 1/2, multicenter, open-label, dose-escalation and expansion trial evaluating NVL-520 as an oral monotherapy. The Phase 1 dose-escalation portion of the study is open and enrolling patients with advanced ROS1-positive solid tumors who have been previously treated with at least one prior ROS1 tyrosine kinase inhibitor (TKI) therapy, and will evaluate the overall safety and tolerability of NVL-520 as well as determine the recommended Phase 2 dose (RP2D), characterize the pharmacokinetic profile, and evaluate preliminary anti-tumor activity.

Once a safe and tolerable dose is determined as the RP2D, the trial is designed to transition directly into the Phase 2 multiple cohort expansion portion, which will evaluate the overall activity of NVL-520 in patients with advanced ROS1-positive NSCLC and other advanced solid tumors. The Phase 2 portion will examine several cohorts of patients based on the number and type of prior anti-cancer therapies they have received. The Phase 2 cohorts are designed to support potential registration in ROS1-positive patients with NSCLC who are kinase inhibitor-naïve and in those who have been previously treated with ROS1 kinase inhibitors.

"Nuvalent thoughtfully designed the ARROS-1 trial to support the goal of seamless acceleration from first-in-human dose-exploration of NVL-520 into Phase 2 cohorts that are structured to evaluate multiple opportunities for potential registration," said Darlene Noci, A.L.M., Senior Vice President of Product Development & Regulatory Affairs for Nuvalent. "Through parallel evaluation of NVL-520 in TKI-naïve and clearly defined cohorts of pre-treated patients, we aim to generate data to comprehensively evaluate NVL-520 throughout the treatment paradigm for ROS1-driven cancers."

In addition to NVL-520, Nuvalent is advancing a robust pipeline including the development of NVL-655 as a parallel lead program for the potential treatment of patients with ALK-positive NSCLC, along with multiple discovery-stage research programs.

"Our focus in 2022 is on establishing Nuvalent as an operationally efficient, clinical-stage biotech company with an active in-house R&D pipeline. We are on track for the planned IND submission for NVL-655 which we expect to enable the opening of our second Phase 1/2 clinical trial for enrollment in the first half of the year, and continue to plan for portfolio expansion with multiple internally discovered novel drug candidates," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "Through the prioritization of a pipeline of novel small molecules designed to overcome the dual challenges of kinase resistance and selectivity, we aim to deliver new medicines that may not only provide additional therapeutic options, but have the potential to advance earlier in the treatment paradigm and become best-in-class treatments for patients with cancer."

Nuvalent ended 2021 with $288.4 million in cash, cash equivalents and marketable securities (unaudited), which, based on its current operating plans, is expected to fund its operations into 2024.

About NVL-520

NVL-520 is a brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit ROS1 over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients with ROS1-mutant variants. NVL-520 is currently being investigated in the ARROS-1 study, a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.

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.