Interstitial Lung and Liver Disease

The various components of the deal bring the total value up to $2.2 billion. Sanofi has taken a surgical approach to its latest piece of M&A, agreeing to pay $1.7 billion to buy Inhibrx for below the market price but then spin out all but one of its candidates to create a new publicly traded biotech. The French pharma wants to get its hands on INBRX-101, a human recombinant protein that Inhibrx is testing in a registration-enabling alpha-1 antitrypsin deficiency (AATD) trial. Rather than swallow Inhibrx whole, Sanofi has decided to spin off the biotech's three anticancer molecules to create a new company that will start life with $200 million in cash and no debt. Inhibrx has accepted an offer of $30 per share, below its $33.33 closing price yesterday. The below-market price reflects the fact Sanofi is only buying one molecule. Inhibrx shareholders will also gain stakes in the new biotech, plus the chance to receive a further $5 a share if a regulatory milestone is met. The various components of the deal bring the total value up to $2.2 billion. Sanofi will have an 8% stake in the new biotech, which will continue to be called Inhibrx and be led by the current CEO Mark Lappe. Once the deal closes in the second quarter, the new Inhibrx will look much like the old Inhibrx, minus its AATD candidate, and Sanofi will have sated its appetite for a rare disease candidate. That candidate, INBRX-101, is on course (PDF) to reach the initial readout from its registration trial around the end of the year. Inhibrx designed the clinical trial to show the effect of INBRX-101 on levels of serum functional AAT, the protective protein that is found at low levels in people with the rare disease. Patients currently receive weekly augmentation with AAT derived from plasma donors to partly offset the deficiency. INBRX-101 is designed to end reliance on donations, reduce dosing frequency and normalize AAT levels. The biotech believes improved diagnosis may quadruple the size of the AATD market in the coming years, creating a $4 billion opportunity that could overwhelm the availability of the plasma products sold by CSL Behring, Grifols and Takeda. Other companies could reduce the need for AAT protein by targeting the cause of the disease but multiple players have struggled to move the needle so far. AATD causes liver and lung disease, with Inhibrx’s registration trial targeting the latter population. Mereo BioPharma has a lung disease candidate, alvelestat, that is on the cusp of phase 3. Vertex, which wants to address both the liver and the lung, gave up on a pair of AATD candidates but is trying again with a third asset, VX-634, that is in phase 1. Wave Life Sciences has a GSK-partnered RNA editing candidate. BioMarin, Intellia Therapeutics and Peak Bio are in the hunt, too, but Sanofi's head of R&D Houman Ashrafian said he sees INBRX-101 as fitting the Big Pharma's focus on “differentiated and potential best-in-class products.”

Preparing for imminent submission of clinical trial applications (CTAs) for GalNAc-conjugated AATD candidate (WVE-006), the industry’s first RNA editing clinical candidate Novel DMD therapeutic candidate (WVE-N531) with best-in-class exon skipping clinical data is on track to enter a potentially registrational Phase 2 clinical study in 2H 2023, with dystrophin data expected in 2024 “R&D Day” virtual event planned for September 28, 2023; will focus on Wave’s leading RNA editing capability and highlight its current and future pipeline of transformative RNA medicines Cash and cash equivalents of $173.0 million as of June 30, 2023, with runway expected into 2025, plus additional potential milestone payments from GSK collaboration in 2023 and beyond Investor conference call and webcast at 8:30 a.m. ET today CAMBRIDGE, Mass., Aug. 03, 2023 (GLOBE NEWSWIRE) -- WAVE Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage RNA medicines company committed to delivering life-changing treatments for people battling devastating diseases, today announced financial results for the second quarter ended June 30, 2023, and provided a business update. “In the second quarter, we continued to rapidly advance our pipeline of RNA medicines towards meaningful inflection points. We are on the cusp of moving the industry’s first RNA editing therapeutic candidate, WVE-006 for alpha-1 antitrypsin deficiency or AATD, into the clinic, which will mark an important milestone not only for Wave, but also for individuals living with AATD and the entire RNA medicines field. WVE-006 has the potential to transform the standard of care for people living with AATD, and the goal of our initial clinical trial will be delivering early clinical proof-of-concept via measurement of validated serum surrogate markers,” said Paul Bolno, MD, MBA, President and Chief Executive Officer of Wave Life Sciences. “While we were disappointed to discontinue WVE-004 for C9-ALS and FTD in the second quarter, we did see successful translation of our preclinical pharmacodynamic effects to clinical biomarker effects, including robust, sustained reductions of up to 50% in poly(GP) with multiple doses. These results are also important validation of our PN chemistry, which is encouraging for our current and upcoming clinical programs, including in DMD, HD, and AATD.” Dr. Bolno continued: “Momentum is building rapidly in our collaboration with GSK, which kicked off at the start of this year, and we are actively working on multiple targets while leveraging proprietary genetic insights through the collaboration. We are excited to share new data on RNA editing disease targets at our annual ‘R&D Day’ virtual event in September. Wave is well-capitalized to leverage our unique, multimodal platform to develop novel RNA medicines and deliver on a steady cadence of clinical data through 2024 and beyond.” Recent Business Highlights Presented new preclinical data for WVE-006 supporting its potential to be a first-and best-in-class treatment for alpha-1 antitrypsin deficiency (AATD). In May 2023, at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, Wave presented data demonstrating that treatment with WVE-006 improved several markers of liver disease in mice, including a decrease in liver inflammation and hepatocyte turnover and reduction in the size of PAS-D positive globules. WVE-006 is uniquely designed to address both liver and lung disease related to AATD and is poised to be the industry’s first RNA editing candidate to reach the clinic. The company expects to submit clinical trial applications (CTAs) for WVE-006 imminently. Highlighted clinical data for WVE-N531 to DMD community at Parent Project Muscular Dystrophy (PPMD)AnnualConference. In June 2023, in an oral presentation at the PPMD Conference, Wave highlighted its clinical data from the proof-of-concept study of WVE-N531, including the highest level of exon skipping seen in any DMD trial, high muscle concentrations, and a safe and tolerable profile. Wave is on track to initiate dosing in Part B, a potentially registrational Phase 2 trial of WVE-N531, in 2023, which will be powered to evaluate functional dystrophin expression following 24 and 48 weeks of biweekly dosing. The primary endpoint will be dystrophin protein levels, and the study will also evaluate safety and tolerability, pharmacokinetics, and functional endpoints. Data are expected in 2024. If successful, WVE-N531 has potential to become a near-term wholly owned commercial opportunity for Wave and would enable accelerated development of additional exon skipping candidates for other mutations. Multi-dose portion of SELECT-HD study of WVE-003 for HD underway. In the second quarter, Wave initiated the multi-dose portion of its ongoing Phase 1b/2a SELECT-HD clinical trial of WVE-003 (allele-selective silencing oligonucleotide) for Huntington’s disease, and dosing is currently underway. Emerging best-in-class siRNA designs highlighted at ASGCT. Also at the May 2023 ASGCT Annual Meeting, Wave highlighted its novel siRNA formats in a poster presentation titled “PN modification of stereopure GalNAc-siRNAs enhances durability of human HSD17B13 silencing in transgenic mouse model.” Wave’s GalNAc-siRNAs were more potent and had better durability of effect in mice compared with reference GalNAc-siRNA designs, which were driven by improved Ago2 loading. These data were also included in Wave’s Nucleic Acids Research publication from April 2023, which can be accessed here. Wave Life Sciences added to Russell Indexes. In June 2023, the company joined the Russell 2000® and Russell 3000® Indexes as part of the annual reconstitution. Anticipated Upcoming Milestones and Events WVE-N531 for DMD: Initiate dosing in Part B of potentially registrational Phase 2 clinical trial in 2023 Deliver data from Part B in 2024 WVE-006 for AATD: Submit CTAs for first-in-human study in 2H 2023 WVE-003 for HD: Deliver additional single-dose and available multi-dose biomarker and safety clinical data in 2H 2023 Platform and Pipeline: “R&D Day” virtual event to be held on September 28, 2023, during which Wave will demonstrate how it is continuing to extend its leadership in RNA editing and share preclinical data on new wholly owned programs Advance collaboration activities with GSK, with potential for additional cash inflows in 2023 and beyond Second Quarter 2023 Financial Results Wave reported a net loss of $21.1 million in the second quarter of 2023, as compared to $41.3 million in the same period in 2022. The decrease in net loss year-over-year was primarily driven by revenue recognized under the company’s collaboration with GSK, which became effective January 27, 2023. Revenue recognized under the GSK and Takeda collaborations in the second quarter of 2023 was $22.1 million. During the second quarter of 2022, revenue of $0.4 million was recognized under the Takeda collaboration. Research and development expenses were $33.3 million in the second quarter of 2023, as compared to $29.7 million in the same period in 2022. The increase in research and development expenses was primarily due to increased external expenses related to Wave’s clinical programs. General and administrative expenses were $12.3 million in the second quarter of 2023, as compared to $12.8 million in the same period in 2022, primarily due to a decrease in share-based compensation. As of June 30, 2023, Wave had $173.0 million in cash and cash equivalents, as compared to $88.5 million as of December 31, 2022. The company expects that its current cash and cash equivalents will be sufficient to fund operations into 2025. Investor Conference Call and Webcast Wave will host an investor conference call today at 8:30 a.m. ET to review second quarter 2023 financial results and pipeline updates. A webcast of the conference call can be accessed by visiting “Investor Events” on the investor relations section of the Wave Life Sciences website: . Analysts planning to participate during the Q&A portion of the live call can join the conference call at the following audio-conferencing link: available here. Once registered, participants will receive the dial-in information. Following the live event, an archived version of the webcast will be available on the Wave Life Sciences website. About Wave Life Sciences Wave Life Sciences (Nasdaq: WVE) is a clinical-stage RNA medicines company committed to delivering life-changing treatments for people battling devastating diseases. Wave aspires to develop best-in-class medicines across multiple therapeutic modalities using PRISM, the company’s proprietary discovery and drug development platform that enables the precise design, optimization, and production of stereopure oligonucleotides. Driven by a resolute sense of urgency, the Wave team is targeting a broad range of genetically defined diseases so that patients and families may realize a brighter future. To find out more, please visit and follow Wave on Twitter @WaveLifeSci. Forward-Looking Statements This press release contains forward-looking statements concerning our goals, beliefs, expectations, strategies, objectives and plans, and other statements that are not necessarily based on historical facts, including statements regarding the following, among others: the anticipated initiation, site activation, patient recruitment, patient enrollment, dosing, generation of data and completion of our clinical trials, and the announcement of such events; the protocol, design and endpoints of our clinical trials; the future performance and results of our programs in clinical trials; future preclinical activities and programs; regulatory submissions; the progress and potential benefits of our collaborations; the potential achievement of milestones under our collaborations and receipt of cash payments therefor; the potential of our preclinical data to predict the behavior of our compounds in humans; our identification and expected timing of future product candidates and their therapeutic potential; the anticipated benefits of our therapeutic candidates compared to others; our ability to design compounds using multiple modalities and the anticipated benefits of that approach; the breadth and versatility of PRISM; the expected benefits of our stereopure oligonucleotides compared with stereorandom oligonucleotides; the potential benefits of our RNA editing capability, including our AIMers, compared to others; the status and progress of our programs relative to potential competitors; anticipated benefits of our proprietary manufacturing processes and our internal manufacturing capabilities; the benefit of nucleic acid therapeutics generally; the strength of our intellectual property and the data that support our IP; the anticipated duration of our cash runway; our intended uses of capital; and our expectations regarding any potential global macro events beyond our control on our business. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including the following: our ability to finance our drug discovery and development efforts and to raise additional capital when needed; the ability of our preclinical programs to produce data sufficient to support our clinical trial applications and the timing thereof; the clinical results of our programs and the timing thereof, which may not support further development of our product candidates; actions of regulatory authorities and their receptiveness to our adaptive trial designs, which may affect the initiation, timing and progress of clinical trials; our effectiveness in managing regulatory interactions and future clinical trials; the effectiveness of PRISM; the effectiveness of our RNA editing capability and our AIMers; our ability to demonstrate the therapeutic benefits of our candidates in clinical trials, including our ability to develop candidates across multiple therapeutic modalities; our dependence on third parties, including contract research organizations, contract manufacturing organizations, collaborators and partners; our ability to manufacture or contract with third parties to manufacture drug material to support our programs and growth; our ability to obtain, maintain and protect our intellectual property; our ability to enforce our patents against infringers and defend our patent portfolio against challenges from third parties; competition from others developing therapies for the indications we are pursuing; our ability to maintain the company infrastructure and personnel needed to achieve our goals; and the information under the caption “Risk Factors” contained in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) and in other filings we make with the SEC from time to time. We undertake no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances. WAVE LIFE SCIENCES LTD. UNAUDITED CONSOLIDATED BALANCE SHEETS (In thousands, except share amounts) June 30, 2023 December 31, 2022 Assets Current assets: Cash and cash equivalents $ 172,974 $ 88,497 Prepaid expenses 9,012 7,932 Other current assets 2,722 2,108 Total current assets 184,708 98,537 Long-term assets: Property and equipment, net of accumulated depreciation of $40,423 and $37,846 as of June 30, 2023, and December 31, 2022, respectively 14,983 17,284 Operating lease right-of-use assets 24,805 26,843 Restricted cash 3,668 3,660 Other assets 1,821 62 Total long-term assets 45,277 47,849 Total assets $ 229,985 $ 146,386 Liabilities, Series A preferred shares and shareholders’ equity (deficit) Current liabilities: Accounts payable $ 12,379 $ 16,915 Accrued expenses and other current liabilities 10,429 17,552 Current portion of deferred revenue 111,133 31,558 Current portion of operating lease liability 6,285 5,496 Total current liabilities 140,226 71,521 Long-term liabilities: Deferred revenue, net of current portion 104,540 79,774 Operating lease liability, net of current portion 28,875 32,118 Other liabilities 190 190 Total long-term liabilities 133,605 112,082 Total liabilities $ 273,831 $ 183,603 Series A preferred shares, no par value; 3,901,348 shares issued and outstanding at June 30, 2023, and December 31, 2022 $ 7,874 $ 7,874 Shareholders’ equity (deficit): Ordinary shares, no par value; 98,566,816 and 86,924,643 shares issued and outstanding at June 30, 2023, and December 31, 2022, respectively $ 839,675 $ 802,833 Additional paid-in capital 124,601 119,442 Accumulated other comprehensive income (loss) (150 ) (29 ) Accumulated deficit (1,015,846 ) (967,337 ) Total shareholders’ equity (deficit) $ (51,720 ) $ (45,091 ) Total liabilities, Series A preferred shares and shareholders’ equity (deficit) $ 229,985 $ 146,386 WAVE LIFE SCIENCES LTD. UNAUDITED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (In thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue $ 22,106 $ 375 $ 35,035 $ 2,125 Operating expenses: Research and development 33,314 29,733 64,293 57,203 General and administrative 12,265 12,806 24,500 25,180 Total operating expenses 45,579 42,539 88,793 82,383 Loss from operations (23,473 ) (42,164 ) (53,758 ) (80,258 ) Other income, net: Dividend income and interest income, net 2,251 124 4,124 150 Other income, net 118 744 1,125 998 Total other income, net 2,369 868 5,249 1,148 Loss before income taxes (21,104 ) (41,296 ) (48,509 ) (79,110 ) Income tax provision — — — — Net loss $ (21,104 ) $ (41,296 ) $ (48,509 ) $ (79,110 ) Net loss per share attributable to ordinary shareholders—basic and diluted $ (0.20 ) $ (0.62 ) $ (0.47 ) $ (1.25 ) Weighted-average ordinary shares used in computing net loss per share attributable to ordinary shareholders—basic and diluted 105,462,414 66,479,293 103,768,971 63,514,426 Other comprehensive loss: Net loss $ (21,104 ) $ (41,296 ) $ (48,509 ) $ (79,110 ) Foreign currency translation (100 ) (142 ) (121 ) (228 ) Comprehensive loss $ (21,204 ) $ (41,438 ) $ (48,630 ) $ (79,338 ) Investor Contact: Kate Rausch +1 617-949-4827 krausch@wavelifesci.com Media Contact: Alicia Suter +1 617-949-4817 asuter@wavelifesci.com

Korro Bio and Frequency Therapeutics announced Friday that they plan to merge in an all-stock transaction. The combined company will operate under the name Korro Bio and focus on the advancement of Korro’s existing portfolio of RNA editing programmes.Korro Bio said it has secured commitment to a planned concurrent $117 million financing and the combined company will have approximately $170 million in cash and equivalents. This should provide a financing runway into 2026, the company added.Korro’s lead programme is an investigational, potentially disease-modifying therapy for the treatment of alpha-1 antitrypsin deficiency (AATD). AATD is an inherited genetic disorder that can cause severe progressive lung and liver disease due to a lack of normal alpha-1 antitrypsin protein (A1AT). Korro Bio’s preclinical product is designed to restore production of normal A1AT and the company intends to submit a regulatory filing allowing it to start a clinical trial in the second half of 2024. Advancement of the programme has been funded in part by a series B financing worth $116 million 18 months ago.Further analysis -- Spotlight On: The growing universe of RNA editing technologiesBy comparison, Frequency Therapeutics saw its share price drop 80% in February after announcing that its potential treatment for sensorineural hearing loss (SNHL) FX-322 failed in a Phase IIb study. The setback prompted Frequency to terminate development of a second potential SNHL treatment candidate, reduce the size of its workforce by 55% and explore ways to raise financing. At the time the company said it would priortise development of a remyelination programme for the treatment of multiple sclerosis but it was confirmed today that development has been discontinued and strategic alternative for the programme ahead of the proposed merger with Korro will be sought.