On July 28, 2022 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported it has completed the safety review of the fourth cohort in a dose escalation clinical trial evaluating Annamycin for the treatment of soft tissue sarcoma (STS) lung metastases, thus concluding the Phase 1b portion of its U.S. Phase 1b/2 clinical trial (Press release, Moleculin, JUL 28, 2022, View Source [SID1234617084]). Preliminary results from the study continue to document clinical activity for Annamycin in the treatment of STS. The safety review committee (SRC) has deemed the dose of 390 mg/m2 to be safe after conclusion of the fourth cohort. Notwithstanding that there was safety at this dose level, tolerability issues present at the 390 mg/m2 dose level caused delays in follow-on cycles and the reduction of subsequent doses, suggesting that a Recommended Phase 2 Dose (RP2D) below 390 mg/m2 was warranted.

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With this in mind and with the recommendation of the SRC, the Company has determined that the RP2D will be 360 mg/m2 for the first three subjects in the Phase 2 portion of the study. The SRC will then review the clinical safety data at this dose and determine whether the RP2D should be further reduced to 330 mg/m2 prior to proceeding with the additional 22 subjects. In addition to continuing to assess safety, including gathering additional information about short-term side effects and possible risks, this Phase 2 portion of the study will also explore the efficacy of Annamycin as a single agent for the treatment of subjects with STS lung metastases for whom prior chemotherapy has failed, and for whom new chemotherapy is considered appropriate.

In the Phase 1b portion of the study, 15 subjects were enrolled and treated per the protocol in four cohorts to determine the maximum tolerable dose and/or the RP2D. Each cohort had three subjects, except for the fourth cohort, which (per the protocol) was expanded to six subjects after a dose-limiting toxicity (DLT) occurred in a single subject. The Company concluded the Phase 1b portion after the fourth cohort of 390 mg/m2 was documented to be safe. Up to 28 subjects, to account for potential over enrollment, will be enrolled at the RP2D in Phase 2 to focus more on quantifying efficacy as well as providing additional safety information.

"As we end the Phase 1b portion of this trial, the preliminary data continue to be encouraging," said Moleculin Chairman and CEO Walter Klemp. "Of the fifteen subjects treated per the protocol, two continue with treatment, and eight subjects have been followed without evidence of disease progression for two months or greater, with three of the eight free of disease progression for 120 days or more. These data are early-stage, and we look forward to developing confirmatory data from future studies. However, based on the data available thus far, we believe Annamycin has the potential to bring a new and effective treatment option to patients with significant unmet needs."

Mr. Klemp added, "We’re also encouraged by the pace of recruitment to date for this trial. To have completed the Phase 1b in just over one year was faster than we expected, especially for a rare disease like STS lung metastases. This is encouraging as we open the Phase 2 portion of the study."

The summary of interim Phase 1b data, which are preliminary and subject to change, from the four cohorts of the study are as follows:

First Cohort (210 mg/m2):

Two subjects received 6 cycles of Annamycin, initially having stable disease, and were then discontinued due to progressive disease.
One subject received 1 cycle, but then discontinued from the study because of a Dosing Delay greater than the time between doses permitted by the protocol. At the End of Study scan performed 39 days post initiation of treatment, the subject had stable disease. The subject was followed and continued to exhibit disease free progression up to 61 days after treatment, at which point the subject began a different therapy.
Second Cohort (270 mg/m2):

In one subject, the end of cycle 2 scan showed a partial response (≥30% reduction in tumor size), and when scanned at the end of cycle 4 the subject showed stable disease. The subject subsequently discontinued from the study, electing to undergo surgical resection to potentially eradicate the disease. The subject is continuing to be followed and at the last follow-up no disease progression was reported at 272 days.
One subject was discontinued from the study when the end of cycle 2 scan revealed progressive disease.
One subject received 1 cycle of treatment and discontinued treatment due to a Dosing Delay. The End of Study scan revealed progressive disease.
Third Cohort (330 mg/m2):

One subject received 1 cycle and was discontinued when an interim, unscheduled scan revealed progressive disease.
One subject was discontinued from the study when the end of cycle 2 scan revealed progressive disease.
One subject was treated with 2 cycles and the end of cycle 2 scan revealed stable disease. The subjected elected to withdraw from receiving any further treatment. The subject was followed and no disease progression was reported at 146 days. The subject elected at that time to discontinue from further follow-up in the study.
Fourth Cohort (390 mg/m2):
Efficacy data for this cohort are incomplete as not all subjects have received their scans and treatment is ongoing.

One subject received 3 cycles of treatment without evidence of any DLTs, with the last 2 cycles at a reduced dose of 292 mg/m2 due to a drug tolerability issue that did not qualify as a DLT. The subject exhibited stable disease at the end of cycle 2. The subject showed progressive disease in the end of treatment scan on the 78th day.
One subject was discontinued from the study after 2 cycles with cycle 2 administered at a reduced dose of 292 mg/m2. The subject discontinued receiving cycles because of a DLT of febrile neutropenia, and the cohort was expanded per the protocol. The end of cycle 2 scan revealed stable disease. The subject initiated additional therapy unrelated to the study on the 68th day and will continue to be followed for Overall Survival.
One subject received 3 cycles of treatment without evidence of any DLTs, with the last 2 cycles administered at reduced doses, due to drug tolerability. The subject exhibited stable disease at the end of cycle 2. The subject showed progressive disease in an unscheduled scan on the 79th day.
One subject received 4 cycles without evidence of any DLTs, with the last three cycles administered at a reduced dose of 292 mg/m2, due to drug tolerability. The end of cycle 4 scans revealed stable disease. The subject is ongoing in the study.
One subject received 3 cycles without evidence of any DLTs, with the last two cycles administered at a reduced dose of 292 mg/m2, due to drug tolerability. The end of cycle 2 scans revealed stable disease. The subject is ongoing in the study.
One subject received 1 cycle without evidence of any dose-limiting toxicities and is ongoing in the study.
One subject received a markedly lower dose than the specified 390 mg/m2 in a protocol violation by the site, also without evidence of any DLTs. That subject’s safety data, but not efficacy, is deemed to be evaluable in the study.
"Consistent with our earlier and ongoing acute myeloid leukemia trials, in the subjects evaluated to date we have seen a complete absence of cardiotoxicity in our trials," Mr. Klemp said. "Again, these are early-stage data, but we’re seeing consistent results in this regard across our Annamycin studies, and we think they’re important because, even though anthracyclines are considered a cornerstone chemotherapy for many types of cancer including STS lung metastases, all currently approved anthracyclines are significantly cardiotoxic. Annamycin was designed to overcome this problem and we believe it has the potential to become the first non-cardiotoxic anthracycline approved for use. If these data continue and our product is approved, Annamycin may not only reduce the risk of many current anthracycline treatment regimens, but it could also enable longer treatment periods with reduced concern for cardiac risk."

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of soft tissue sarcoma, in addition to Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia. For more information about the Phase 1b/2 study evaluating Annamycin for the treatment of STS lung metastases, please visit clinicaltrials.gov and reference identifier NCT04887298.

Study Design
In Phase 1b, Annamycin was administered as an intravenous (IV) infusion over 2 hours on Day 1, followed by 20 days off (1 cycle = 21 days). Subjects visit the study site every 21 days (±3 days) at which time safety monitoring – including for adverse events (AEs), as well as a physical examination, laboratory evaluations (clinical chemistry, complete blood count), vital signs, weight measurements, Eastern Cooperative Oncology Group (ECOG) performance status, and electrocardiograms (ECGs) – is performed, followed by an IV infusion of study drug. Cardiac function is followed by echocardiogram (ECHO) scans at screening, at the end of the first two cycles and then following every other cycle thereafter, at the End of Treatment visit, and if feasible, during follow up at 6 months (±1 month) and 1 year (±1 month) after study drug discontinuation. As long as the Investigator considers that the benefits of treatment with Annamycin continue to outweigh the risks, treatment will continue every 21 days until tumor progression is observed or unacceptable toxicity occurs.

Tumor response is monitored every 6 weeks (±1 week) from Cycle 1 Day 1 during treatment, at the End of Treatment visit, and then every 3 months (±1 month) until disease progression using RECIST 1.1 criteria. Those subjects who leave the study after a maximum response is achieved and who do not start another therapy will be followed every 3 months (±1 month) for progression-free survival (PFS). If a subject receives further therapy after discontinuing from the study, they will be followed only for overall survival (OS) and if feasible, follow-up ECHO scans at 6 months (±1 month) and 1 year (±1 month) will be conducted after study drug discontinuation.

About Annamycin
Annamycin is the Company’s next-generation anthracycline that has been shown in animal models to accumulate in the lungs at up to 30-fold the level of doxorubicin. Importantly, Annamycin has also demonstrated a lack of cardiotoxicity in multiple early-stage human clinical trials, including ongoing trials for the treatment of acute myeloid leukemia (AML) and STS lung metastases. For that reason, although additional data will be necessary, the Company believes Annamycin may not face the same usage limitations imposed on doxorubicin, one of the most common currently approved anthracyclines. Annamycin is currently in development for the treatment of AML and STS lung metastases and the Company believes the drug may have the potential to treat additional indications.

On July 28, 2022 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported financial results for the second quarter of 2022 (Press release, Merck & Co, JUL 28, 2022, View Source [SID1234617083]).

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"I continue to be immensely proud of how the Merck team is performing in all facets of our business — scientifically, commercially and operationally," said Robert M. Davis, chief executive officer and president. "Our strategy is working and our future is bright. I am very confident that we are well-positioned to achieve our near- and long-term goals, anchored by our commitment to deliver innovative medicines and vaccines to patients and value to all of our stakeholders, including shareholders."

Financial Summary

Financial information presented in this release reflects Merck’s results on a continuing operations basis, which excludes Organon & Co. that was spun-off on June 2, 2021.

Generally accepted accounting principles (GAAP) earnings per share (EPS) assuming dilution was $1.55 for the second quarter of 2022. Non-GAAP EPS of $1.87 for the second quarter of 2022 excludes acquisition- and divestiture-related costs, restructuring costs, as well as income and losses from investments in equity securities. In 2022, the company changed the treatment of certain items for purposes of its non-GAAP reporting. Results for 2021 have been recast to conform to the new presentation, which reduced previously reported second-quarter 2021 non-GAAP EPS of $1.31, resulting in revised non-GAAP EPS of $0.61. For more information, refer to the Form 8-K filed by the company on April 21, 2022.

Year-to-date results can be found in the attached tables.

Vaccines Program Highlights

The FDA approved an expanded indication for VAXNEUVANCE (Pneumococcal 15-valent Conjugate Vaccine) to include infants and children. VAXNEUVANCE is now indicated to help prevent invasive pneumococcal disease caused by the serotypes in the vaccine in individuals six weeks and older.
The CDC Advisory Committee on Immunization Practices unanimously voted to provisionally recommend use of VAXNEUVANCE as an option to the currently available 13-valent pneumococcal conjugate vaccine (PCV13) for children under 19 years according to currently recommended PCV13 dosing and schedules. These provisional recommendations will be reviewed by the director of the CDC and the Department of Health and Human Services, and final recommendations will become official when published in the CDC’s Morbidity and Mortality Weekly Report.
Merck presented positive results from the Phase 1/2 study for V116, Merck’s investigational Pneumococcal 21-Valent Conjugate Vaccine designed to target serotypes that account for 85% of all invasive pneumococcal diseases in U.S. adults 65 years and older as of 20193, and enrolled the first patient into the Phase 3 STRIDE-3 trial evaluating V116 in vaccine-naïve adults. V116 contains eight serotypes not included in any currently licensed pneumococcal vaccine.
Oncology Program Highlights

Merck announced the following regulatory milestones for KEYTRUDA (pembrolizumab):
The FDA accepted an application seeking approval for KEYTRUDA as adjuvant therapy for stage IB (>4 centimeters), II or IIIA non-small cell lung cancer (NSCLC) following complete surgical resection based on data from the Phase 3 KEYNOTE-091 trial. The FDA has set a Prescription Drug User Fee Act date of January 29, 2023, however further data may be provided during the review process that may delay this date.
The EC approved four indications for KEYTRUDA:
Approved as monotherapy for the adjuvant treatment of adult and adolescent patients (>12 years of age) with stage IIB or IIC melanoma and who have undergone complete resection, based on results from the KEYNOTE-716 trial. The EC also approved expanding the indication for KEYTRUDA in advanced and stage III melanoma to include adolescent patients 12 years and older.
Approved in combination with chemotherapy as neoadjuvant treatment, and then continued as adjuvant monotherapy after surgery, for adults with locally advanced or early-stage triple-negative breast cancer (TNBC) at high risk of recurrence, based on results from the KEYNOTE-522 trial.
Approved as monotherapy for the treatment of certain adult patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors for five types of cancer: unresectable or metastatic colorectal, gastric, small intestine or biliary cancer, as well as advanced or recurrent MSI-H/dMMR endometrial cancer, based on results from the KEYNOTE-164 and KEYNOTE-158 trials.
Approved in combination with chemotherapy, with or without bevacizumab, for patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (Combined Positive Score ≥ 1), based on results from the KEYNOTE 826 trial.
The European Medicines Agency Committee for Medicinal Products for Human Use adopted a positive opinion for Lynparza (olaparib), an oral poly (ADP-ribose) polymerase (PARP) inhibitor being co-developed and co-commercialized with AstraZeneca, as adjuvant treatment for patients with germline BRCA-mutated, human epidermal growth factor 2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy, based on results from the Phase 3 OlympiA trial.
At the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Merck presented new data in more than 25 types of cancer and held an investor event to highlight key data and provide updates from its late-stage development programs and diverse early-stage pipeline.
Global Pharmaceuticals Program Highlight

Merck, in collaboration with Ridgeback Biotherapeutics, announced data from a pre-specified exploratory analysis for LAGEVRIO (molnupiravir) from the Phase 3 MOVe-OUT study indicating that a lower proportion of participants treated with LAGEVRIO had an acute care visit or COVID-19-related acute care visit versus placebo. Additionally, in a post-hoc subgroup analysis, fewer LAGEVRIO-treated patients who were hospitalized post-randomization in MOVe-OUT required respiratory interventions (including invasive mechanical ventilation) compared to those who received placebo.
Second-Quarter Revenue Performance

The following table reflects sales of the company’s top pharmaceutical products, as well as sales of Animal Health products.

Pharmaceutical Revenue

Second-quarter pharmaceutical sales increased 28% to $12.8 billion. Pharmaceutical sales growth in the second quarter was 16% excluding LAGEVRIO sales, and was primarily driven by oncology, vaccines and hospital acute care products. The COVID-19 pandemic unfavorably affected sales in the second quarter of 2021 by approximately $400 million, which favorably impacted the growth rate in the second quarter of 2022.

LAGEVRIO sales totaled $1.2 billion for the second quarter, primarily consisting of sales in Japan and the U.K. The initial commitment of LAGEVRIO to the U.S. was fulfilled in the first quarter of 2022.

Growth in oncology was largely driven by higher sales of KEYTRUDA, which rose 26% to $5.3 billion in the quarter. Global sales growth of KEYTRUDA reflects continued strong momentum from metastatic indications including certain types of NSCLC, renal cell carcinoma, head and neck squamous cell carcinoma, TNBC and MSI-H cancers, and increased uptake across recent earlier-stage launches including certain types of neoadjuvant/adjuvant TNBC in the U.S.

Also contributing to higher sales in oncology was a 28% increase in Lenvima (lenvatinib) alliance revenue driven primarily by higher demand in the U.S., and an 11% increase in Lynparza alliance revenue reflecting continued demand globally, particularly in the U.S. driven by strong uptake in earlier-stage breast cancer.

Growth in vaccines was primarily driven by higher combined sales of GARDASIL (Human Papillomavirus Quadrivalent [Types 6, 11, 16 and 18] Vaccine, Recombinant) and GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) vaccines to prevent certain cancers and other diseases caused by human papillomavirus (HPV). Second-quarter GARDASIL/GARDASIL 9 sales grew 36% to $1.7 billion primarily driven by strong demand outside of the U.S., particularly in China, which also benefited from increased supply.

Growth in hospital acute care reflects higher demand globally for BRIDION (sugammadex) injection 100 mg/mL, a medicine for the reversal of neuromuscular blockade induced by rocuronium bromide or vecuronium bromide in adults and pediatric patients aged 2 years and older undergoing surgery. Sales increased 10% to $426 million, primarily due to an increase in its share among neuromuscular blockade reversal agents and an increase in surgical procedures during the second quarter. Growth in hospital acute care also reflects higher sales of ZERBAXA (ceftolozane and tazobactam), a combination cephalosporin antibacterial and beta-lactamase inhibitor for the treatment of adults with certain bacterial infections. Sales of $46 million resulted from the phased resupply initiated in the fourth quarter of 2021 that is being expanded to additional markets during 2022.

Pharmaceutical sales growth was partially offset by lower combined sales of ISENTRESS/ISENTRESS HD (raltegravir), an HIV integrase inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 infection, which declined 24% to $147 million reflecting lower global demand. Pharmaceutical sales growth was also partially offset by lower combined sales of JANUVIA (sitagliptin) and JANUMET (sitagliptin and metformin HCI), which declined 2% to $1.2 billion, primarily reflecting the unfavorable effect of foreign exchange and lower pricing in certain international markets, partially offset by the impact of a prior year unfavorable adjustment to rebate reserves in the U.S. The company lost market exclusivity for JANUVIA and JANUMET in China in July and will lose market exclusivity in the European Union in September.

Animal Health Revenue

Animal Health sales totaled $1.5 billion for the second quarter of 2022, flat compared to the second quarter of 2021. Excluding the unfavorable effect from foreign exchange, Animal Health sales grew 5%. Sales were driven primarily by livestock products reflecting higher demand globally for ruminant and poultry products. Sales in companion animal products were primarily driven by the BRAVECTO (fluralaner) parasiticide line of products.

Second-Quarter Expense, EPS and Related Information

GAAP Expense, EPS and Related Information

Gross margin was 71.1% for the second quarter of 2022 compared to 72.8% for the second quarter of 2021. The decrease primarily reflects impacts from LAGEVRIO, which has a lower gross margin due to profit sharing with Ridgeback, as well as higher inventory write-offs, higher manufacturing costs and higher acquisition- and divestiture-related costs. The gross margin decline was partially offset by the favorable effects of product mix.

Selling, general and administrative (SG&A) expenses were $2.5 billion in the second quarter of 2022, an increase of 10% compared to the second quarter of 2021. The increase primarily reflects higher promotion and administrative costs, including compensation and benefit costs, as well as higher acquisition- and divestiture-related costs, partially offset by the favorable impact of foreign exchange.

Research and development (R&D) expenses were $2.8 billion in the second quarter of 2022 compared to $4.3 billion in the second quarter of 2021. The decrease was primarily driven by a $1.7 billion charge in the prior year for the acquisition of Pandion Therapeutics, Inc. (Pandion). The decline was partially offset by higher clinical development spending, higher compensation and benefits, and higher investments in technology in support of the digital enablement of Merck’s research operations.

Other (income) expense, net, was $438 million of expense in the second quarter of 2022 compared to $103 million of income in the second quarter of 2021, primarily due to net unrealized losses from investments in equity securities in the second quarter of 2022, compared to net unrealized income from investments in equity securities in the second quarter of 2021. Other (income) expense, net, in the second quarter of 2022 also reflects higher pension settlement costs of approximately $100 million compared to the second quarter of 2021.

The effective income tax rate was 12.0% for the second quarter of 2022 compared to 29.3% in the second quarter of 2021. The effective income tax rate in the second quarter of 2021 reflects no tax benefit recognized on the charge for the acquisition of Pandion.

GAAP EPS was $1.55 for the second quarter of 2022 compared to $0.48 for the second quarter of 2021.

Non-GAAP Expense, EPS and Related Information

Non-GAAP gross margin was 74.7% for the second quarter of 2022 compared to 76.5% for the second quarter of 2021. The decrease in non-GAAP gross margin primarily reflects impacts from LAGEVRIO, which has a lower gross margin due to profit sharing with Ridgeback, as well as higher inventory write-offs and manufacturing costs. The gross margin decline was partially offset by the favorable effects of product mix.

Non-GAAP SG&A expenses were $2.4 billion in the second quarter of 2022, an increase of 7% compared to the second quarter of 2021. The increase primarily reflects higher promotion and administrative costs, including compensation and benefit costs, partially offset by the favorable impact of foreign exchange.

Non-GAAP R&D expenses were $2.8 billion in the second quarter of 2022 compared to $4.3 billion in the second quarter of 2021. The decrease primarily reflects a $1.7 billion charge in the prior year for the acquisition of Pandion. The decline was partially offset by higher clinical development spending, higher compensation and benefits, and higher investments in technology in support of the digital enablement of Merck’s research operations.

Non-GAAP other (income) expense, net, was $202 million of expense in the second quarter of 2022 compared to $38 million of expense in the second quarter of 2021 reflecting higher pension settlement costs of approximately $100 million.

The non-GAAP effective income tax rate was 13.8% for the second quarter of 2022 compared to 26.7% in the second quarter of 2021. The non-GAAP effective income tax rate in the second quarter of 2021 reflects no tax benefit recognized on the charge for the acquisition of Pandion.

Non-GAAP EPS was $1.87 for the second quarter of 2022 compared to $0.61 for the second quarter of 2021.

A reconciliation of GAAP to non-GAAP net income and EPS is provided in the table that follows.

Financial Outlook

Beginning in 2022, Merck no longer excludes expenses for upfront and milestone payments related to collaborations and licensing agreements, or charges related to pre-approval assets obtained in transactions accounted for as asset acquisitions from its non-GAAP results. Historically, the company excluded these charges to the extent they were considered by the company to be significant to the results of a particular period. These changes were made to align with views expressed by the U.S. Securities and Exchange Commission. Prior periods have been recast to reflect this change. For 2021, non-GAAP results have been recast to include $1.7 billion of incremental R&D expense, resulting in revised full-year 2021 EPS of $5.37.

Business development continues to be a priority for Merck, as demonstrated by the company’s recent collaboration with Orion announced in July for the development and commercialization of ODM-208, an investigational steroid synthesis inhibitor for the treatment of metastatic castration-resistant prostate cancer. The GAAP and non-GAAP financial outlooks include the upfront payment of $290 million, which will have an estimated $0.09 negative impact on full-year EPS.

As an on-going practice, the financial outlook will not include significant potential business development transactions.

Merck continues to experience strong global underlying demand across its key pillars of growth, particularly in oncology and vaccines. As a result, Merck is raising and narrowing its full-year guidance for sales.

At mid-July 2022 exchange rates, Merck expects sales growth of 18% to 20% in 2022, with full-year sales estimated to be between $57.5 billion and $58.5 billion, including a negative impact from foreign exchange of approximately 3%, a greater than 1% incremental negative impact from prior sales guidance.

Merck’s estimated full-year non-GAAP effective income tax rate is unchanged and expected to be between 13.5% and 14.5%.

Merck expects its estimated full-year 2022 GAAP EPS to be between $5.89 and $5.99.

Merck is narrowing its expected full-year 2022 non-GAAP EPS range to be between $7.25 and $7.35, including a negative impact from foreign exchange of approximately 3% at mid-July exchange rates. Operational strength of approximately $0.25 that would have resulted in an increase from the previous guidance range is being offset by the following negative impacts:

The upfront payment of $290 million to Orion
A greater than 1% incremental negative impact from foreign exchange
Higher U.S. pension settlement expense
The non-GAAP range excludes acquisition- and divestiture-related costs and costs related to restructuring programs as well as income and losses from investments in equity securities.

The company continues to expect sales of $5.0 billion to $5.5 billion from LAGEVRIO for full-year 2022. Merck shares profits equally with its partner, Ridgeback, which is reflected in cost of sales.

Earnings Conference Call

Investors, journalists and the general public may access a live audio webcast of the call today at 8:00 a.m. EDT on Merck’s website.

Participants may join the call by dialing 877-692-8955 (USA Toll-Free) or 234-720-6979. If you are calling from other countries, visit this weblink. All dial-in participants can use the access code 1857604. Journalists who wish to ask questions are requested to contact a member of Merck’s Media Relations team.

On July 28, 2022 MaaT Pharma (EURONEXT: MAAT – the "Company"), a French clinical-stage biotech and a pioneer in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to improving survival outcomes for patients with cancer, reported its cash position as of June 30, 2022, and its revenues for the second quarter of 2022 (Press release, MaaT Pharma, JUL 28, 2022, View Source [SID1234617082]).

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"The second quarter of 2022 saw further progress in our pipeline and the achievement of a crucial milestone for MaaT Pharma. The announcement of data showing a satisfactory safety profile and robust engraftment for MaaT033, our second drug candidate, opens an attractive market opportunity to expand the development to a wider patient population as we focus on preventing complications in patients receiving allo-HSCT[2] and in haematological malignancies overall," said Hervé Affagard, CEO and co-founder of MaaT Pharma.

Second quarter operational and clinical highlights

Clinical development

In June 2022, the Company confirmed positive results from its Phase 1b study evaluating MaaT033, the Company’s second drug candidate, in blood cancer patients; the clinical trial was completed early due to promising interim results.
MaaT Pharma also indicated that preparations are on track for the upcoming Phase 2/3 trial to evaluate MaaT033’s efficacy in improving overall survival and preventing complications in patients with blood cancers receiving allogeneic hematopoietic stem cell transplantation; based on current plans, this study is expected to start in Q4 2022.
In Europe, MaaT013, the Company’s leading drug candidate, is currently being evaluated in two clinical trials launched in Q1 2022, which are moving forward according to the Company’s expected timelines:
Phase 3 open label, single arm trial for drug candidate MaaT013 in the treatment of acute Graft-versus-Host Disease: in addition to France, Germany, and Spain where the trial is ongoing, the Company has received regulatory approvals to start the clinical trial in Austria and Belgium. An interim review of preliminary data is expected in the first half of 2023.
Phase 2a trial, sponsored by AP-HP[3], evaluating MaaT013 in combination with immune checkpoint inhibitors for patients with melanoma, is ongoing.
In the US, interactions with the U.S. Food and Drug Administration (FDA) are ongoing regarding MaaT013, for which US development is currently on clinical hold.
Operational highlights

On May 31, 2022, MaaT Pharma held its annual general meeting. For further information, please visit: View Source
On June 7, 2022, the Company hosted its first virtual R&D Day conference, attended by 150 participants. The replay is accessible here: View Source
"Over the first half of 2022 we are proud to have delivered to our shareholders the operational and clinical milestones set out at the time of our IPO. Our cash position remains solid, providing us with a cash runway through Q3 2023 by which time we expect to have interim data from our Phase 3 trial of MaaT013, and the first patient treated with MaaT033 in a Phase 2/3," stated Siân Crouzet, CFO and COO of MaaT Pharma.

Cash position1

As of June 30, 2022, total cash and cash equivalents were EUR 38.4 million, as compared to EUR 41.1 million as of March 31, 2022, and EUR 43.3 million as of December 31, 2021. The net change in cash over the first half of 2022 was EUR 4.9 million, including EUR 2.7 million in bank loans from BNP Paribas and Caisse d’Epargne Rhone Alpes (CERA) received over the course of the second quarter of 2022. Additional draws down, up to 4.4 million euros, are expected to be made by the end of 2022 from existing facilities signed with CIC and Bpifrance. The Company believes it has sufficient cash to cover needs of the development programs up until the end of the third quarter of 2023.

Revenues in Q2 20221

MaaT Pharma reported revenues[4] from its compassionate access program of EUR 0.2 million for the quarter ended June 30, 2022, compared with EUR 0.3 million for the first quarter of 2022. Total revenues for the first half of 2022 amount to EUR 0.5 million compared with EUR 0.4 million for the first half of 2021. In 2021, revenues were invoiced as of February 2021 whereas in 2022 the Company benefits from a full 6 months of revenues.

Upcoming financial communication and investor conference participation

September 12-14, 2022 – C. Wainwright 24th Annual Global Investment Conference
September 15-16, 2022 – KBC Securities Life Sciences Conference
September 28, 2022 – 5th edition – Forum LPB Valeurs Régionales
September 29, 2022 – Half-year Results 2022*
October 6-7, 2022 – Investor Access Event
*Indicative calendar that may be subject to change.

[1] Unaudited data
[2] Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment of liquid tumors which affect approximately 22,000 patients every year in the 7 major markets
[3] AP-HP: Assistance Publique – Hôpitaux de Paris
[4] Revenues correspond to compensation invoiced in relation to the compassionate access program, as approved by the French National Drug Safety Agency (Agence Nationale de Sécurité du Médicament or ANSM).

On July 28, 2022 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) ("Lexicon") reported the pricing of its previously announced underwritten public offering of 16,843,600 shares of its common stock, par value $0.001 (the "Common Stock"). The shares of Common Stock are being offered at a public offering price of $2.50 per share (Press release, Lexicon Pharmaceuticals, JUL 28, 2022, View Source [SID1234617081]). All of the shares are being offered by Lexicon. The gross proceeds from the public offering are expected to be approximately $42.1 million, before deducting underwriting discounts and commissions and other offering expenses. In addition, Lexicon has granted the underwriters a 30-day option to purchase up to an additional 2,526,540 shares of Common Stock (the "Option Shares") at the public offering price, less underwriting discounts and commissions. The public offering is expected to close on or about August 1, 2022, subject to the satisfaction of customary closing conditions.

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Lexicon currently intends to use the net proceeds that it will receive from the public offering and the concurrent private placement, together with its existing cash and cash equivalents and short-term investments, for (i) funding pre-commercial and commercial launch activities for sotagliflozin in heart failure; (ii) funding continued development of sotagliflozin in heart failure and LX9211 in neuropathic pain; and (iii) working capital and other general corporate purposes.

Citigroup and Piper Sandler are acting as joint book-running managers for the public offering.

In addition to the shares being sold in the underwritten public offering, Lexicon has agreed to sell 17,156,400 shares of its Common Stock to raise gross proceeds of approximately $42.9 million in a concurrent private placement at $2.50 per share to one or more affiliates (the "Private Placement Purchasers") of Invus, L.P., Lexicon’s largest stockholder. The Private Placement Purchasers will have the option to purchase, on a pro rata basis, up to an additional 2,573,460 shares of Common Stock at the public offering price of $2.50 per share to the extent the underwriters exercise their option to purchase the Option Shares. The sale of these shares of Common Stock will not be registered under the Securities Act of 1933, as amended (the "Securities Act"). The concurrent private placement is also scheduled to close on August 1, 2022, subject to the satisfaction of customary closing conditions. The closing of the underwritten public offering is not conditioned on the closing of the concurrent private placement.

A shelf registration statement on Form S-3 relating to the underwritten public offering was filed with the U.S. Securities and Exchange Commission ("SEC") on August 6, 2021 and declared effective by the SEC on September 14, 2021. The shares of Common Stock proposed to be issued in the concurrent private placement have not been registered under the Securities Act, or the securities laws of any state or other jurisdiction in the United States, and may not be offered, pledged, sold, delivered or otherwise transferred, directly or indirectly, in the United States except pursuant to registration under the Securities Act, or an applicable exemption from the registration requirements of the Securities Act and, in each case, in compliance with other applicable securities laws. A preliminary prospectus supplement and accompanying prospectus relating to the underwritten public offering have been filed with the SEC and are available on the SEC’s website at www.sec.gov. A final prospectus supplement and accompanying prospectus will be filed with the SEC. When available, copies of the final prospectus supplement and accompanying prospectus may also be obtained from Citigroup Global Markets Inc., c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at 1-800-831-9146, or by email at [email protected]; or Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, Attn: Prospectus Department, by telephone at 1-800-747-3924, or by email at [email protected].

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, these securities, nor will there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale is not permitted.

On July 28, 2022 Leidos (NYSE: LDOS), a FORTUNE 500 science and technology leader, reported that it will participate in the Jefferies Industrials Conference being held in New York, NY (Press release, Leidos, JUL 28, 2022, View Source [SID1234617080]).

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Roger Krone, Chief Executive Officer, will engage in a question and answer "fireside chat" on Tuesday, Aug. 9, 2022, at 3:30 p.m. ET.

A live audio webcast of the event will be available on the Leidos Investor Relations website at View Source . A replay of the webcast will be available following the presentation at the same link listed above for 90 days afterward.