On August 4, 2022 Merck KGaA reported its half-yearly financial report (Presentation, Merck KGaA, AUG 4, 2022, View Source [SID1234618590]).

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On August 4, 2022 Kyowa Hakko Kirin reported its consolidated financial summary fiscal 2022 second quarter results (Presentation, Kyowa Hakko Kirin, AUG 4, 2022, View Source [SID1234618961]).

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On August 4, 2022 Portage Biotech reported An initial readout of an ongoing phase 1/2 study (ISRCTN80472712) from the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting indicated that treatment with IMM60 in patients with advanced melanoma and non–small cell lung cancer (NSCLC) yielded promising preliminary safety data, according to lead author Nick Coupe, MBBS, PhD (Press release, Portage Biotech, AUG 4, 2022, View Source [SID1234619258]).

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Aside from reporting that no adverse effects occurred in the 5 patients who were treated, Coupe, a consultant medical oncologist at Churchill Hospital, highlighted a notable reduction in tumor volume for 1 patient and a mixed response in another. Although the work is early, he explained how the research may lay the groundwork for further research.

"The hope is that we demonstrate yet another way of enhancing antitumor immune responses," Coupe explained. "There is obviously a lot of work in this field, [including] a lot of existing work looking at new targets. This is quite a novel approach. It’s not targeting a specific checkpoint; it’s targeting a component of the immune system that has a broad effect. It is quite a novel approach. By doing so, hopefully we can complement existing therapies with PD-1 [inhibitors]. There may be rationale to combine this with other treatments. Hopefully, it does lead to some excitement and yet another element of immunotherapy research in a clinical setting."

In an interview with CancerNetwork, Coupe highlighted the mechanism of action of the novel synthetically derived agonist of invariant natural killer cells formulated in the PORT-2 liposome and what future research efforts might look like.

CancerNetwork: Could you start off by telling me about the rationale for this study?
Coupe: The rationale stems from an unmet need in both tumor groups. We we’re looking at patients with metastatic melanoma and non–small cell lung cancer. It’s well known that there have been some big advances, particularly in the field of melanoma, in recent years. Despite that, close to 50% of patients with metastatic disease will eventually succumb. For those patients who require optimal treatments, combination immunotherapy has [a roughly] 60% grade 3 toxicity rate; it’s quite a toxic treatment.

In lung cancer, immunotherapy has been a big step forward with PD-1 inhibition, but in this group, the outcomes are still very poor, with only around 20% to 30% of people experiencing long-term survival. There’s a big unmet need, and the rationale for this study stems from some preclinical work that goes back a number of years. IMM60 is a molecule that was discovered Oxford. It has a broad impact upon the immune system targeting various components. The hope is that it can synergize with the therapies that are already in existence so that we may capitalize on the gains that are already made.

What is the mechanism of action of IMM60?
It’s an invariant, natural Killer T-cell agonist. Natural killer T cells are a subset of the T-cell population in the body. [They aren’t] as well studied as other subsidiaries, but they basically carry a very important function that affects multiple arms of the immune system. It has been known for some time that patients with high levels of invariant natural kill T-cell activation have more favorable cancer outcomes. PORT-2 is an activator of this population. It has direct impact against tumors in terms of upregulating PD-L1 expression, which we know is favorable because it can enhance the effectiveness of existing therapies. It is also a potent activator of not just natural killer cells, but also antigen-progenitor cells and CD8 T cells, which are the effector cells that drive antitumor responses. There is also some evidence that it helps create a favorable tumor microenvironment, potentially overcoming some of the resistance mechanisms that [lead to certain patients failing to derive] benefit from existing therapies.

At this year’s meeting, what findings read out from this study?
[Data were read-out from] two-thirds of the phase 1 study population, so it is very much in the in the early phases of development. We’re still in the dose-escalation phase. We presented the results of 5 patients who have been treated so far for dose level 3 and dose level 1, and 2 patients were in the in the second dose level. What we have seen so far for the 5 patients treated was 1 mixed response with the second dose and there was a quite impressive tumor reduction in a number of sites. In this particular case, as I just referenced, a mediastinum mass [went] from 4 cm down to 1.9 cm in a patient who was heavily pretreated with all existing standard therapies for melanoma. We also saw from a toxicity point of view that the treatment was safe. It only caused a very low number of grade 1 or grade 2 toxicities, so it’s very well tolerated. We’ve seen no SAEs [serious adverse effects] or AEs requiring any specific intervention.

Where do you see future efforts being focused here?
We aim to complete the dose-escalation study soon. We’re recruiting and hope to follow patients at their current dose level. Once we complete the dose-escalation phase, we’ll start our safety phase where we will be giving IMM60 PORT-2 alongside pembrolizumab [Keytruda]. Once we’ve completed the safety cohort, the next phase is to move into a phase 2 study. In this part of the study, we’re going to recruit over 80 patients from a number of different sites where we’ll be comparing a combination of PORT-2 and pembrolizumab vs pembrolizumab alone in patients with advanced melanoma and [NSCLC who] have not been pretreated.

Reference
Coupe N, Walters IB, Kramer RA, et al. A phase 1 first-in-human dose finding/randomized phase 2 study of IMM60 and pembrolizumab (PEM) in advanced melanoma and non–small cell lung cancer (NSCLC; IMP-MEL). J Clin Oncol. 2022;40(suppl 16):2582. doi:10.1200/JCO.2022.40.16_suppl.2582

On August 4, 2022 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), reported its second quarter 2022 financial results (Press release, Synta Pharmaceuticals, AUG 4, 2022, View Source [SID1234617455]).

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Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "We believe resmetirom, a once-daily oral medication that targets the steatohepatitis and resulting fibrosis in the liver, has the potential to transform the treatment of NASH. As we enter an important period for the company, I’m confident in our strategic plan and operational readiness: we’ve continued to advance our Phase 3 MAESTRO program, expanded our market development activities in the U.S., and improved our financial position with the term loan agreement announced last quarter. Madrigal is well-positioned for the road ahead."

Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, "The MAESTRO-NAFLD-1 results we recently presented at EASL reinforce our understanding of the favorable safety and tolerability profile of resmetirom, and we remain on track for topline data from the pivotal MAESTRO-NASH biopsy study in the fourth quarter. These studies are intended to serve as the foundation for a new drug application filing for resmetirom in the noncirrhotic NASH population in the first half of next year."

Remy Sukhija, Chief Commercial Officer of Madrigal, added, "As we continue to lay the foundation for a potential first-to-market launch in the U.S., our engagement with key stakeholders has accelerated in recent months. In June we launched the ‘NASH Explored’ disease education campaign for healthcare providers and announced expanded partnerships with key patient advocacy groups. Additionally, our Market Access and Medical Affairs teams have conducted NASH disease education sessions with payers that together account for more than 80% of all branded prescriptions in the U.S. All stakeholder groups recognize the serious unmet need for approved therapies to treat NASH with liver fibrosis and extensive market research has reinforced our confidence in the commercial potential of resmetirom."

Financial Results for the Six Months Ended June 30, 2022

As of June 30, 2022, Madrigal had cash, cash equivalents and marketable securities of $211.8 million, compared to $270.3 million at December 31, 2021. The decrease in cash and marketable securities resulted primarily from cash used in operations of $107.3 million, partially offset by the capital raised under the Loan Facility ("Loan Facility") with Hercules Capital, Inc. ("Hercules").

Operating expenses were $70.3 million and $127.9 million for the three month and six month periods ended June 30, 2022, compared to $61.7 million and $114.7 million in the comparable prior year periods.

Research and development expenses for the three and six month periods ended June 30, 2022 were $58.5 million and $106.4 million, compared to $51.6 million and $97.4 million in the comparable prior year periods. The increase is attributable primarily to additional activities related to the Phase 3 clinical trials, and an increase in head count.

General and administrative expenses for the three and six month periods ended June 30, 2022 were $11.8 million and $21.4 million, compared to $10.1 million and $17.3 million in the comparable prior year periods. The increase is due primarily to increases in commercial preparation activities, including an increase in headcount and an increase in non-cash stock compensation.

Interest income for the three and six month periods ended June 30, 2022 was $0.3 million and $0.4 million, compared to $0.1 million and $0.3 million in the comparable prior year periods. The increase in interest income was due primarily to a higher average interest rates in 2022.

Interest expense for the three and six month periods ended June 30, 2022 was $0.8 million and $0.8 million, compared to $0 million and $0 million in the comparable prior year periods. The increase in interest expense was as a result of the Loan Facility we entered with Hercules.

About the Resmetirom Phase 3 Registration Program for the Treatment of NASH

Madrigal is currently conducting two Phase 3 clinical trials, MAESTRO-NASH and MAESTRO-NAFLD-1, to demonstrate the safety and efficacy of resmetirom for the treatment of NASH.

MAESTRO-NASH is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of resmetirom in patients with liver biopsy-confirmed NASH and was initiated in March 2019. The study targeted enrollment of 900 patients with biopsy-proven NASH (fibrosis stage 2 or 3, at least 450 fibrosis stage 3), randomized 1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. After 52 weeks of treatment, a second biopsy is performed. The dual primary surrogate endpoints on biopsy are NASH resolution with ≥2-point reduction in NAS (NAFLD Activity Score), and with no worsening of fibrosis OR a 1-point decrease in fibrosis with no worsening of NASH. Either primary endpoint can be achieved for a successful trial outcome. A key secondary endpoint is lowering of LDL-C. The planned target enrollment was announced as completed on June 30, 2021.

The first 900 patients in the MAESTRO-NASH study will continue on therapy after the initial 52-week treatment period; up to another 1,100 patients are to be added using the same randomization plan. The study is expected to continue for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation events.

MAESTRO-NAFLD-1 was initiated in December 2019 and the 52-week multicenter, randomized, placebo-controlled Phase 3 study of resmetirom in over 1,200 patients with NAFLD, presumed NASH, has completed the double-blind arms and an open-label 100 mg arm. An additional open-label active treatment arm in patients with early (well-compensated) NASH cirrhosis is ongoing. The primary endpoint is to evaluate the safety and tolerability of resmetirom. An open-label extension study (MAESTRO-NAFLD-OLE) is ongoing.

Patients in the 52-week phase of MAESTRO-NAFLD-1 were randomized 1:1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, placebo in double-blind arms or resmetirom 100 mg in an open-label arm. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH), did not include a liver biopsy and represents a "real-life" NASH study. Patients with 3 metabolic risk factors were documented with NASH or NAFLD by historical liver biopsy or noninvasive techniques. Using noninvasive measures, MAESTRO-NAFLD-1 was designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular- and liver-related endpoints. These key secondary endpoints included LDL-C, apolipoprotein B, and triglyceride lowering; and reduction of liver fat as determined by MRI-PDFF. Additional secondary and exploratory endpoints were assessed including reduction in liver enzymes, FibroScan, and MRE scores and other NASH biomarkers.

Data from the 52-week portion of MAESTRO-NASH, together with data from MAESTRO-NAFLD-1 and other data, including safety parameters, will form the basis for a potential subpart H submission to FDA for accelerated approval of resmetirom for treatment of NASH.

In May 2022, Madrigal announced plans to expand the resmetirom development program by initiating MAESTRO-NASH Outcomes, a randomized double-blind placebo-controlled study in approximately 700 patients with early NASH cirrhosis to allow for noninvasive monitoring of progression to liver decompensation events. A positive outcome is expected to support the full approval of resmetirom for noncirrhotic NASH, potentially accelerating the timeline to full approval. In addition, this study has the potential to broaden the label for resmetirom to include NASH patients with compensated cirrhosis.

On August 4, 2022 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell therapy to treat cancer, reported financial results for the second quarter ended June 30, 2022 and provided a business update (Press release, Adaptimmune, AUG 4, 2022, View Source [SID1234617476]). For the three months ended June 30, 2022, Revenue was $5.5 million, Total Operating Expenses (Research and Development and General and Administrative) were $49.3 million, and Net Loss was $44.5 million.

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"We continue to demonstrate progress with our four focus areas for 2022: submitting our BLA for afami-cel, building a MAGE-A4 franchise, scaling up manufacturing capabilities, and advancing our allogeneic platform, pipeline and collaborations," said Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer. "The data presented at ASCO (Free ASCO Whitepaper) further confirm the potential of afami-cel for the initial indication of synovial sarcoma with the BLA submission on-track for Q4 this year. To support commercialization of afami-cel and other products both near- and longer-term, we are investing in focused but scalable operational infrastructure to set us up for success. At the same time, we are carefully monitoring market conditions. We will continue to prudently manage expenses and stop or delay non-core activities."

Adaptimmune’s first potential commercial product, afami-cel, supported by positive data readouts

Biologics License Application (BLA) submission for afami-cel on track for Q4 2022

Adaptimmune is preparing its BLA and continues to target submission to the U.S. Food and Drug Administration (FDA) in the fourth-quarter 2022 for the treatment of synovial sarcoma. This BLA is supported by data from Cohort 1 of the pivotal trial SPEARHEAD-1, which met its primary endpoint for efficacy. In addition, the Company has the following progress updates:

●Miltenyi Biotec vector facility released for cGMP manufacture
●Vector and T-cell product characterization nearing completion
●Method validation for commercial T-cell lot release assays (including potency assays) in progress
●Vector process performance qualification (PPQ) initiated
●Pre-market approval (PMA) for the companion diagnostic is on-track to be submitted simultaneously with BLA

Afami-cel presentation at ASCO (Free ASCO Whitepaper) 2022 – responses reported across all patient subgroups

As reported in June, data based on pooled analyses of characteristics associated with clinical responses (per investigator assessment) from both Cohort 1 of the SPEARHEAD-1 trial, as well as the Phase 1 trial of afami-cel in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma (MRCLS), were presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper)

●Overall response rate was 36% in heavily pre-treated patients across both types of sarcomas (41% in synovial sarcoma and 10% for MRCLS), with a median duration of response of 52 weeks
●Patients who responded to afami-cel had longer progression-free survival (median 58 weeks) compared to non-responders (median 12 weeks)

●Responses occurred across all clinical subgroups, with greater response rates associated with lower baseline tumor burden, fewer prior lines of therapy, and higher MAGE-A4 expression
●Benefit:risk profile of afami-cel has been favorable, to date

Potential of next-gen MAGE-A4 targeted cell therapy in multiple solid tumors

Phase 1 signal-finding SURPASS trial update at ESMO (Free ESMO Whitepaper) in September

●The purpose of the next-generation ADP-A2M4CD8 program is to improve the potency of Adaptimmune’s first-generation product targeting MAGE-A4, afami-cel, to achieve meaningful clinical responses beyond sarcoma
●ADP-A2M4CD8 is being investigated in the SURPASS family of trials
●Last year, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2021 Congress, Adaptimmune reported data from 22 evaluable patients with confirmed responses in ovarian, head and neck, esophagogastric junction, and bladder cancers from the Phase 1 signal-finding SURPASS trial, with this next-generation cell therapy
●Based on positive signals in gastroesophageal cancers in the Phase 1 SURPASS trial, Adaptimmune initiated a Phase 2 SURPASS-2 trial last year
●The Company plans to initiate an additional Phase 2 trial, SURPASS-3, this year for people with ovarian cancer, based on positive signals from the SURPASS Phase 1 trial
●On September 10, 2022 at 15:45 CET, Dr. David Hong from the MD Anderson Cancer Center, will present a data update from the Phase 1 signal-finding SURPASS trial at the ESMO (Free ESMO Whitepaper) 2022 Congress
●Data at ESMO (Free ESMO Whitepaper) will include 44 patients who received ADP-A2M4CD8 and 43 patients will be evaluable for efficacy (as of the data cut-off date of August 01, 2022)
●On September 9th, the Company will host a live virtual event from 8 a.m. to 9 a.m. EDT to discuss the ESMO (Free ESMO Whitepaper) data and its SURPASS family of trials

Corporate and other news

●Adaptimmune has implemented rigorous cost containment measures to enable delivery against its four key focus areas: submitting the BLA for afami-cel, building its MAGE-A4 franchise, scaling up manufacturing capabilities, and progressing the allogeneic platform
●To prioritize near- and mid-term value creation from its MAGE-A4 franchise, including the BLA submission for afami-cel and the SURPASS family of trials, Adaptimmune will delay submission of an IND for its new next-generation cell therapy ADP-A2M4N7X19, which it is developing in collaboration with Noile-Immune. Core preclinical activities will continue.
●Construction is underway to increase the Company’s cGMP manufacturing space at its Navy Yard site in Philadelphia, PA to support current clinical trials and future commercial products
●A dedicated allogeneic manufacturing facility in the United Kingdom is nearing completion, which will support the IND planned for 2023 for Adaptimmune’s wholly owned allogeneic cell therapy targeting MAGE-A4

Financial Results for the three and six months ended June 30, 2022

●Cash / liquidity position: As of June 30, 2022, Adaptimmune had cash and cash equivalents of $97.8 million and Total Liquidity1 of $258.1 million, compared to $149.9 million and $369.6 million, respectively, as of December 31, 2021.
●Revenue: Revenue for the three and six months ended June 30, 2022 was $5.5 million and $9.1 million, respectively, compared to $3.1 million and $3.5 million for the same periods in 2021. Revenue has increased primarily due to an increase in development activities under our
1 Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below

collaboration arrangements, in particular due to development activities under the Genentech Strategic Collaboration and License Agreement, which become effective in October 2021.
●Research and development (R&D) expenses: R&D expenses for the three and six months ended June 30, 2022 were $34.7 million and $71.5 million, respectively, compared to $28.9 million and $53.4 million for the same periods in 2021. R&D expenses increased due to an increase in the average number of employees engaged in research and development, increases in subcontracted expenditures and increases in in-process research and development costs. These were offset by an increase in reimbursements receivable for research and development tax and expenditure credits.
●General and administrative (G&A) expenses: G&A expenses for the three and six months ended June 30, 2022 were $14.6 million and $31.4 million, respectively, compared to $13.5 million and $27.4 million for the same periods in 2021 due to increases in employee-related costs and other corporate costs.
●Net loss: Net loss attributable to holders of the Company’s ordinary shares for the three and six months ended June 30, 2022 was $44.5 million and $94.8 million, respectively ($(0.05) and $(0.10) per ordinary share), compared to $39.1 million and $76.8 million, respectively ($(0.04) and $(0.08) per ordinary share), for the same periods in 2021.

Financial Guidance

The Company believes that its existing cash, cash equivalents and marketable securities, together with the additional payments under the Strategic Collaboration and License Agreement with Genentech, will fund the Company’s current operations into early 2024, as further detailed in the Company’s Quarterly Report on Form 10-Q for the three and six months ended June 30, 2022, to be filed with the Securities and Exchange Commission following this earnings release.

Conference Call Information

The Company will host a live teleconference and webcast to provide additional details at 8:00 a.m. EDT (1:00 p.m. BST) today, August 4, 2022. A live webcast of the conference call and replay can be accessed at View Source Call in information is as follows: (800)-952-5114 (US or Canada) or +1 (416)-406-0743 (International and additional options available HERE). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (5869059).