Charles River and Valo Launch Logica, an Integrated AI-Powered Drug Discovery Solution to Rapidly Deliver Optimized Preclinical Assets

On April 27, 2022 Charles River Laboratories International, Inc. (NYSE: CRL) and Valo Health, Inc ("Valo") have launched LogicaTM, an artificial intelligence (AI) powered drug solution that directly translates clients’ biological insights into optimized preclinical assets (Press release, Charles River Laboratories, APR 27, 2022, View Source [SID1234613061]). Logica leverages Valo’s AI-powered Opal Computational Platform and Charles River’s leading preclinical expertise, providing clients with transformed drug discovery with a single integrated offering seamlessly translating targets to candidate nomination.

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"Through our partnership with Valo, we’re integrating Charles River’s laboratory capabilities with industry-altering AI-driven molecular design to provide our clients with highly advanceable leads and candidates, while tying client costs to value generation," said Birgit Girshick, Corporate Executive Vice President & Chief Operating Officer, Charles River. "AI-powered solutions are driving drug discovery forward and this is the kind of innovation our industry needs to ultimately bring effective treatments to patients faster."

"Valo is thrilled to partner with Charles River on this first of its kind offering," added David Berry, MD, Ph.D., founder, and CEO of Valo. "We are creating an opportunity to fully outsource small molecule discovery while providing a true risk-sharing model with advanceable leads and candidates with the goal of helping companies scale faster, translating more biological insight into candidates to make better drugs for patients, faster."

Logica’s Advanceable Lead (Logica-AL) and Candidate (Logica-C) programs, which are available exclusively from Charles River, are part of a multi-year strategic partnership that Charles River and Valo announced earlier this year. Logica-AL aims to provide customers with highly advanceable, potent series with desired characteristics, such as in vitro absorption, distribution, metabolism, and excretion (ADME) and selectivity profiles understood. In addition, the Logica-C offering will use the advanceable leads and trained predictive models to rapidly progress the program, ultimately aiming to deliver a development candidate that has undergone necessary safety and efficacy tests and is ready for IND-enabling studies.

Logica utilizes industry-leading predictive models, chemical design and synthesis capabilities, DNA-encoded libraries, in silico high throughput screening from Valo’s Opal Computational Platform as well as Charles River’s leading capabilities in all aspects of discovery optimization including high throughput screening, medicinal chemistry, ADME, biology, pharmacology, and ultimately safety testing and IND submission, joining together for the first time to create a computation-powered, unified target-to-candidate offering. Logica combines approaches that have a demonstrated ability to produce an advanceable lead series 90 percent of the time and deliver development candidates 58 percent of the time. The products will be offered with most of the client cost tied to success.

PTC ANNOUNCES SECOND FISCAL QUARTER 2022 RESULTS

On April 27, 2022 PTC (NASDAQ: PTC) reported financial results for its second fiscal quarter ended March 31, 2022 (Press release, PTC Therapeutics, APR 27, 2022, View Source [SID1234613077]).

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"In the second quarter we continued to see our key operating and financial metrics showing strong performance. We delivered organic constant currency ARR growth of 13% year over year to end Q2 at $1.56 billion. In Q2, our cash from operations was $142 million, up 17% year over year, and our adjusted free cash flow was $158 million, up 22% year over year. The strength in Q2 was broad-based across all segments and geographic regions, driven by demand for digital transformation and SaaS," said James Heppelmann, President and CEO, PTC.

"Our differentiated product portfolio and growing SaaS capabilities position PTC to drive superior value for customers. Our market position coupled with our subscription model, which took us years of hard work to put in place, is highly resilient and positions us to continue to deliver strong double-digit ARR growth. Based on our strong performance in the first half of the year and the momentum we have created, we are raising our fiscal 2022 guidance for ARR and free cash flow," concluded Heppelmann.

Second Quarter 2022 Highlights 1
Key operating and financial highlights are set forth below. For additional details, please refer to the Q2’22 earnings presentation and financial data tables that have been posted to the Investor Relations section of our website at investor.ptc.com. Revenue and, as a result, operating margin and earnings per share are impacted by revenue recognition under ASC 606.

ARR was $1,532 million at the end of Q2’22, up 11% compared to Q2’21. On a constant currency basis, ARR was $1,564 million, up 13% compared to Q2’21, and above guidance of $1,540 million to $1,550 million. ARR at the end of Q2’22 includes a $4 million reduction associated with discontinuing our business operations in Russia.
Cash flow from operations was $142 million, free cash flow was $140 million, and adjusted free cash flow was $158 million in Q2’22, compared to Q2’21 cash flow from operations of $122 million, free cash flow of $116 million, and adjusted free cash flow of $130 million.
Revenue was $505 million in Q2’22 compared to $462 million in Q2’21, representing growth of 9%. On a constant currency basis, year-over-year revenue growth in Q2’22 was 13%.
Operating margin was 32% in Q2’22, compared to 22% in Q2’21. Non-GAAP operating margin in Q2’22 was 42%, compared to 37% in Q2’21. GAAP and non-GAAP operating margin expanded year over year due to higher revenue and operational discipline.
Earnings per share was $0.76 in Q2’22, compared to $0.92 in Q2’21. Non-GAAP earnings per share in Q2’22 was $1.39, compared to $1.08 in Q2’21. GAAP EPS in Q2’22 was negatively impacted by a non-cash charge within other expense due to a decline in value of a publicly traded equity investment, which was sold in Q2’22.
Total cash and cash equivalents as of the end of Q2’22 was $307 million. Gross debt was $1.28 billion as of the end of Q2’22. During Q2’22, we repaid $175 million on our revolving credit facility and we had proceeds of $43 million from the sale of the aforementioned equity investment.
Stock repurchases were $5 million in Q2’22, reflecting the settlement of repurchases that were initiated in Q1’22
1 We include operating and non-GAAP financial measures in our operational highlights. The detailed definitions of these items and reconciliations of non-GAAP financial measures to comparable GAAP measures are included below and in the reconciliation tables at the end of this press release.

Fiscal 2022 and Q3’22 Guidance
"PTC delivered strong second quarter results that exceeded our expectations," said Kristian Talvitie, EVP and CFO, PTC. "Based on our Q2 performance and our forecast for the remainder of the year, we are raising our guidance for fiscal 2022 ARR, Free Cash Flow, and Revenue. Despite significant foreign exchange headwinds and the impact of exiting our business in Russia, our strong execution and operational discipline have helped us to deliver solid financial performance thus far in fiscal 2022, and we believe we are well positioned to deliver on our updated targets for the year."

(1)On a constant currency basis, using our FY’22 Plan foreign exchange rates (rates as of September 30, 2021) for all periods

(2)FY’22 cash from operations and free cash flow guidance include expected restructuring payments of $45 million (current estimate is $40 million to $45 million) and transaction-related payments of approximately $5 million (already incurred in 1H’22), both of which are excluded from FY’22 adjusted free cash flow guidance; Q3’22 cash from operations and free cash flow guidance include expected restructuring payments of approximately $10 million and transaction-related payments of approximately $5 million (already incurred in 1H’22), both of which are excluded from Q3’22 adjusted free cash flow guidance

(3)Free cash flow and adjusted free cash flow guidance are net of expected capex of approximately $25 million (previously $30 million) in FY’22 and $5 million in Q3’22

Our FY’22 and Q3’22 financial guidance includes the assumptions below:

We provide ARR guidance on a constant currency basis, using our FY’22 Plan foreign exchange rates (rates as of September 30, 2021) for all periods. Based on foreign exchange rate fluctuations as of the end of Q2’22, we currently expect a $34 million headwind (previously $13 million), relative to our constant currency ARR guidance for FY’22, and a $32 million headwind, relative to our constant currency ARR guidance for Q3’22.
We expect FY’22 organic churn to improve by approximately 100 basis points over FY’21.
Due to invoicing seasonality, the majority of our collections occur in the first half of our fiscal year. Q4 is our lowest cash flow generation quarter.
Costs are expected to ramp throughout FY’22 due to hiring and increased SaaS investments. At the mid-point of ARR guidance, we expect FY’22 GAAP operating expenses to increase approximately 3% to 4% (previously 4% to 5%) and non-GAAP operating expenses to increase approximately 2% to 3% over FY’21.
FY’22 GAAP results are expected to include the items outlined below, totalling $293 million to $308 million (previously $275 million to $280 million), as well as their related tax effects:
$160 million to $170 million of stock-based compensation expense (previously $178 million)
$58 million of intangible asset amortization expense
$35 million to $40 million of restructuring charges (previously $40 million to $45 million)
$35 million of FY’22 net realized losses from the sale of an equity investment (new)
Approximately $5 million of transaction-related charges (new)
Our FY’22 guidance does not reflect operating results of the Intland acquisition and the ITCI transaction, the impact of business combination accounting, incremental interest expense, or transaction-related charges not incurred as of the end of Q2’22.
Related to restructuring, for FY’22 we expect:
P&L charges of $35 million to $40 million (previously $40 million to $45 million), of which $32 million was incurred in the first half of FY’22.
Cash outflows for restructuring payments of $40 million to $45 million (previously $45 to $50 million), of which $28 million was paid in the first half of FY’22. We expect the majority of remaining payments to be made in Q3’22. Restructuring payments in FY’22 include $5 million related to prior period actions, primarily the relocation of our headquarters in FY’19.
Our FY’22 GAAP tax rate is expected to be approximately 20% and our non-GAAP tax rate is expected to be approximately 19%.
FY’22 capital expenditures are expected to be approximately $25 million (previously $30 million).
For the remainder of FY’22, we plan to focus on de-levering. In FY’23 and on a go-forward basis, assuming our Debt/EBITDA ratio is below 3x, our goal is to return approximately 50% of our free cash flow to shareholders via share repurchases.
PTC’s Fiscal Second Quarter Results Conference Call
The Company will host a conference call to discuss results at 5:00 pm ET on Wednesday, April 27, 2022. To participate in the live conference call, dial (888) 330-2508 or (240) 789-2735 and provide the passcode 7328695, or log in to the webcast, available on PTC’s Investor Relations website. A replay will also be available.

Important Disclosures
Important Information About Our Non-GAAP Financial Measures
PTC provides supplemental non-GAAP financial measures to its financial results. We use these non-GAAP financial measures, and we believe that they assist our investors, to make period-to-period comparisons of our operating performance because they provide a view of our operating results without items that are not, in our view, indicative of our operating results. These non-GAAP financial measures should not be construed as an alternative to GAAP results as the items excluded from the non-GAAP financial measures often have a material impact on our operating results, certain of those items are recurring, and others often recur. Management uses, and investors should consider, our non-GAAP financial measures only in conjunction with our GAAP results.

Non-GAAP operating expense, non-GAAP operating margin, non-GAAP gross profit, non-GAAP gross margin, non-GAAP net income and non-GAAP EPS exclude the effect of the following items: stock-based compensation; amortization of acquired intangible assets; acquisition-related and other transactional charges included in general and administrative expenses; restructuring and other charges, net; certain non-operating charges and credits; and income tax adjustments. Additional information about the items we exclude from our non-GAAP financial measures and the reasons we exclude them can be found in "Non-GAAP Financial Measures" on page 24 of our Annual Report on Form 10-K for the fiscal year ended September 30, 2021. In FY’21, we incurred tax expense related to a South Korean tax matter which is excluded from our non-GAAP financial measures as it is related to prior periods and not included in management’s view of results for comparative purposes. We also recorded a tax benefit in FY’21 related to the release of our U.S. valuation allowance as a result of the Arena acquisition and our conclusion that it is now more likely than not that we will realize the majority of our deferred tax assets in the U.S. As the non-GAAP tax provision is calculated assuming that there is no valuation allowance, this benefit has been excluded from our non-GAAP financial measures.

Free Cash Flow and Adjusted Free Cash Flow – PTC provides information on free cash flow and adjusted free cash flow to enable investors to assess our ability to generate cash without incurring additional external financings and to evaluate our performance against our announced long-term goals and intent to return approximately 50% of our free cash flow to shareholders via stock repurchases. Free cash flow is cash provided by (used in) operations net of capital expenditures. Adjusted free cash flow is free cash flow net of restructuring payments, acquisition-related payments, and non-ordinary course tax-related payments or receipts. Free cash flow and adjusted free cash flow are not measures of cash available for discretionary expenditures.

Constant Currency (CC) Change Metric – We present CC information to provide a framework for assessing how our underlying business performed excluding the effects of foreign currency rate fluctuations. To present CC information, FY’22 and comparative prior period results for entities reporting in currencies other than United States dollars are converted into United States dollars using the foreign exchange rate as of September 30, 2021, rather than the actual exchange rates in effect during that period.

Operating Measures
ARR – To help investors understand and assess the performance of our business as a SaaS and on-premise subscription company we provide an ARR (Annual Run Rate) operating measure. ARR represents the annualized value of our portfolio of active subscription software, cloud, SaaS, and support contracts as of the end of the reporting period. ARR includes orders placed under our Strategic Alliance Agreement with Rockwell Automation, including orders placed to satisfy contractual minimum commitments.

We believe ARR is a valuable operating metric to measure the health of a subscription business because it captures expected subscription and support cash generation from customers.

Cellectis Receives $20 Million Convertible Note Under Collaboration Agreement with its Partner Cytovia Therapeutics

On April 27, 2022 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that its partner Cytovia Therapeutics, LLC ("Cytovia"), a biopharmaceutical company empowering natural killer ("NK") cells to fight cancer through stem cell engineering and multispecific antibodies, entered into a definitive business combination agreement with Isleworth Healthcare Acquisition Corp. (NASDAQ: ISLE) ("Isleworth"), a Special Purpose Acquisition Company ("SPAC") (Press release, Cellectis, APR 27, 2022, View Source [SID1234613010]).

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Concurrent with the business combination agreement, Cellectis received a $20 million convertible note in payment of the upfront collaboration consideration provided for pursuant to the research collaboration and non-exclusive license agreement entered between Cellectis and Cytovia in February 2021. The terms of the note provide for conversion into common stock of the combined company upon completion of the business combination, which is subject to the satisfaction or waiver of customary closing conditions. In connection with this convertible note, Cellectis received a warrant to purchase additional shares of the combined company representing up to 35% of the shares issued upon conversion of the note at a predetermined exercise price, with the number of shares issuable upon exercise and the exercise subject to certain adjustments.

« We are impressed by the progress Cytovia has accomplished in the past months. Cytovia shares Cellectis’ mission to provide life-saving off-the-shelf allogeneic cell therapies to patients, and we are excited to be providing them with best-in-class TALEN gene editing for cell therapy applications. Congratulations to the Cytovia team for this transaction, which is an important milestone as they continue their journey to progress gene-edited NK therapeutics towards a cure for cancer! » said André Choulika, CEO of Cellectis.

Cellectis and Cytovia’s research and development collaboration:

In February 2021, Cellectis and Cytovia entered into a strategic research and development collaboration to develop TALEN gene-edited iPSC NK and CAR-NK cells. In November 2021, Cellectis and Cytovia extended their collaboration to include new CAR target and development in China by Cytovia’s strategic partner, CytoLynx Therapeutics.

Financial terms of the collaboration include the $20 million convertible note as well as up to $805 million of development, regulatory, and sales milestones and single-digit royalty payments on the net sales of all partnered products commercialized by Cytovia.

Cellectis is developing custom TALEN, which Cytovia uses to edit iPSCs. Cytovia is responsible for the differentiation and expansion of the gene-edited iPSC master cell bank into NK cells and is conducting the pre-clinical evaluation, clinical development, and commercialization of the mutually-agreed-upon selected therapeutic candidates. Cellectis has granted Cytovia a worldwide license under the patent rights over which Cellectis has control in this field, including in China, in order for Cytovia to modify NK cells to address multiple gene-targets for therapeutic use in several cancer indications.

HiFiBiO Therapeutics to Present Trial in Progress Poster for HFB200301 at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting

On April 27, 2022 HiFiBiO Therapeutics, a multinational clinical-stage biotherapeutics company, reported that clinical trial investigator, Alexander I Spira, MD, PhD, FACP, Co-Director of the Virginia Cancer Specialists (VCS) Research Institute and Director of the Thoracic and Phase I Program, will present a Trials in Progress Poster for HFB200301 on Sunday, June 5 from 8:00 AM to 11:00 AM CT at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting held June 3 – 7, 2022, in Chicago, IL (Press release, HiFiBiO Therapeutics, APR 27, 2022, View Source [SID1234613029]).

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"HFB200301 is an anti-TNFR2 antibody that induces T cell and natural killer cell activation, demonstrated in preclinical models. The unique mechanism of action indicates that HFB200301 functions as a bridge between innate and adaptive immunity" said Dr. Alexander Spira. "We are excited to have VCS medical staff and patients to be a part of this Phase I clinical study (NCT05238883). Our hospital’s clinical strength combined with HiFiBiO’s innovative DIS approach will hopefully accelerate the clinical development of HFB200301 for cancer patients."

"We look forward to sharing the clinical study for HFB200301, a first-in-class cancer therapeutic targeting TNFR2 as well as our DIS indications selection strategy," said Luigi Manenti, MD, Chief Medical Officer of HiFiBiO Therapeutics. "With strong in-vivo efficacy as a monotherapy and in combination with anti-PD-1 in preclinical models, we believe it has significant potential in DIS selected tumor types including EBV+ gastric cancer, PD-L1+ pleural mesothelioma and clear cell renal cell carcinoma."

Details on the poster presentation are as follows:

Title: Phase I study of HFB200301, a first-in-class TNFR2 agonist monoclonal antibody in patients with solid tumors selected via Drug Intelligent Science (DIS)
Abstract Number: TPS2670
Poster Session: Developmental Therapeutics – Immunotherapy
Session Date and Time: Poster Session 3 – Sunday, June 5 at 8:00 AM – 11:00 AM CT

The abstract will be available through the ASCO (Free ASCO Whitepaper) Meeting Library at View Source on May 26, 2022.

HFB200301 (TNFR2)
HFB200301 is a first-in-class agonistic anti-TNFR2 antibody that binds potently and selectively to TNFR2 and induces the activation of CD4 T cells, CD8 T cells and NK cells. In vivo, HFB200301 demonstrates potent antitumor activity as a single agent and in combination with anti-PD-1. HiFiBiO is applying a biomarker strategy by leveraging its DIS platform to select indications who may benefit the most from HFB200301 treatment.

ASLAN Pharmaceuticals Reports First Quarter 2022 Financial Results and Provides Corporate Update

On April 27, 2022 ASLAN Pharmaceuticals (Nasdaq: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, reported financial results for the first quarter ended March 31, 2022, and provided an update on recent corporate activities (Press release, ASLAN Pharmaceuticals, APR 27, 2022, View Source [SID1234613045]).

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"We have made strong progress in the first quarter of the year with the initiation of TREK-AD, the global Phase 2b trial of eblasakimab, a potential first-in-class antibody targeting the IL-13 receptor, and welcoming new team members to support the late-stage development of eblasakimab," said Dr Carl Firth, CEO, ASLAN Pharmaceuticals. "Following the presentation of the positive data from our proof-of-concept study in the late-breaker session at the American Academy of Dermatology meeting, we plan to publish new data from this study in the coming months to support the potential of eblasakimab as a differentiated therapy for patients with moderate-to-severe AD. By targeting the receptor, and blocking signaling of both IL-13 and IL-4 through the Type 2 receptor, eblasakimab may be effective in a range of other Type 2-driven comorbidities, which is very important in this patient population."

First quarter 2022 and recent business highlights

Q1 and recent clinical developments

In January, the TREK-AD (TRials with EblasaKimab in Atopic Dermatitis) Phase 2b trial was initiated to evaluate the efficacy and safety of eblasakimab in patients with moderate-to-severe AD. The randomized, double-blind, placebo-controlled, multi-center, dose-ranging clinical trial is evaluating five treatment arms (four active treatment arms and one placebo arm) and is expected to enroll approximately 300 patients across sites in North America, Europe and Asia Pacific. Topline data from the study is expected in the first half of 2023.
In January, results of an interim analysis of the completed Phase 1b proof-of-concept study of eblasakimab in AD were accepted for poster presentation at the 2022 Winter Clinical Dermatology Conference – Hawaii.
In January, the Company hosted the second episode in its series of Key Opinion Leader (KOL) webinars, the "A4 (Aspects of Atopic Dermatitis and ASLAN004) Series: Dialogues with International Thought Leaders in Dermatology". Dr April Armstrong, MD MPH, discussed the key clinical study parameters likely to impact patient responses and clinical trial outcomes in AD. Replay for the webinar is available here. The replays can also be found on the "Events and Presentations" section in ASLAN’s Investor Relations website.
In March, key efficacy and safety data from the completed Phase 1b proof-of-concept study that demonstrated eblasakimab’s potential to offer a differentiated treatment option for patients were presented in a late-breaker oral session at the 2022 American Academy of Dermatology Annual Meeting. These data confirmed that eblasakimab’s inhibition of the IL-13 receptor, blocking signaling of both IL-13 and IL-4 through the Type 2 receptor, can contribute significantly to reducing inflammation in AD. ASLAN believes that this ‘dual blockade’ may not only offer a differentiated treatment option for patients in terms of safety and dosing regimen, but may also address other allergic comorbidities that many of these patients suffer from.
Corporate updates

In March, Alex Kaoukhov, MD, was appointed as Chief Medical Officer based in the Company’s U.S. office. Alex has more than 20 years of global drug development experience in the U.S. and Europe, and was most recently Head of Clinical Development, Senior Vice President at Bioniz Therapeutics, where he established and managed a team responsible for the development of therapeutic assets for the treatment of skin and gastrointestinal autoimmune diseases. Prior to this, Alex served as Head of Global Development at Almirall, where he oversaw global clinical and non-clinical development programs. He also was responsible for business development activities including the in-licensing of lebrikizumab for Europe. Prior to Almirall, Alex was Associate Vice President of Clinical Development at Allergan and served in clinical development leadership roles at Novartis and Galderma.
Anticipated upcoming milestones

Initiation of Phase 2 study of farudodstat, also known as ASLAN003, in inflammatory bowel disease is planned for the first half of 2022.
New data on biomarkers and patient reported outcome measures from the Phase 1b proof-of-concept study of eblasakimab expected in the second half of 2022.
Topline data from the Phase 2b TREK-AD study of eblasakimab is expected in the first half of 2023.
First quarter 2022 financial highlights

As of March 31, 2022, the Company had cash, cash equivalents and short-term investments of $87.4 million.
Cash used in operations for the first quarter of 2022 was US$7.2 million compared to US$7.6 million in the same period in 2021.
Research and development expenses were US$9.4 million in the first quarter of 2022 compared to US$3.8 million in the first quarter of 2021. The increase was driven by clinical development expenses and manufacturing costs related to eblasakimab and the TREK-AD Phase 2b trial.
General and administrative expenses were US$2.5 million in the first quarter of 2022 compared to US$3.1 million in the first quarter of 2021. The decrease was due to financing costs incurred in the first quarter of 2021.
Net loss attributable to stockholders for the first quarter of 2022 was US$12.9 million or $0.19 per ADS compared to a net loss of US$6.7 million or $0.13 per ADS for the first quarter of 2021.
The weighted average number of American Depositary Shares (ADSs) outstanding in the computation of basic loss per share for the first quarter of 2022 was 69.7 million (representing 348.7 million ordinary shares) compared to 51.4 million (representing 257.2 million ordinary shares) for the first quarter of 2021. One ADS is the equivalent of five ordinary shares.