5-MeO-DMT

Pictured: Bottles wrapped in an Iboga plant/Taylor Tieden for BioSpace Notoriously difficult to treat, substance use disorders are devastating individuals and healthcare systems across the globe. They are also a primary target of psychedelic drug developers who believe these novel therapeutics can help turn the tide. In 2018, the total medical costs of substance use disorder among people with U.S. employer-sponsored insurance came to an estimated $35.3 billion. Current treatment options include 12-step groups, detox programs and medicines such as disulfiram and acamprosate for alcohol use disorder (AUD) and buprenorphine for opioid use disorder (OUD). Despite the availability of such treatments, 3.2 million people died globally from SUD-related causes in 2019 alone. Several biopharma companies are placing bets that psychedelic therapies can help curb SUD. There are currently eight psychedelic candidates in development for SUDs, including AUD and OUD, according to Psychedelic Alpha, spanning modalities such as ketamine, psilocybin and DMT. Albert Garcia-Romeu, an associate professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine who studies psilocybin for addiction and other conditions, said the data generated so far “absolutely suggests” that psychedelics can be more effective than traditional treatments for SUDs. But as the field awaits the first FDA approval of a psychedelic for psychiatric use, substantial hurdles remain to development of the drugs for these conditions. Ketamine, LSD and Ibogaine In the 1950s and 1960s, before being outlawed, LSD was studied “heavily” as a potential treatment for SUDs, and “showed some promise in treating alcohol and opioid dependence,” Garcia-Romeu told BioSpace. However, he said, therapeutic research with classic psychedelics then stalled until the 2000s, “and most of the work since that time has really focused on psilocybin,” the active component of magic mushrooms. Other substances, including ketamine and ibogaine, have also shown some promise in treating addiction, he noted. New York–based MindMed is developing MM120, or LSD D-tartrate, for generalized anxiety disorder, among other therapeutic areas. Chief Medical Officer Daniel Karlin told BioSpace that while LSD has historically shown evidence of efficacy in SUD, its mechanism is not fully explained. But, he said, “LSD is neat because it has both a psychiatric psychological mechanism and it has a neurobiological mechanism,” with an acute neurobiological effect leading to an acute psychological experience. “We exist as a story we tell ourselves about ourselves,” Karlin said, “and for some people, that organization leads to neurotic unhappiness,” manifesting in anxiety, depression, or addiction. With LSD treatment, the mind’s organizational structures “come offline,” he explained. “This story you tell about yourself gets disorganized.” During this experience, people have the opportunity to see their narrative differently, Karlin said. After LSD treatment, the organization comes back online, but it comes back differently. Elsewhere, Toronto-based Awakn Life Sciences is in Phase III trials in the U.K. with AWKN-001, an s-ketamine–based therapy to be used in conjunction with cognitive behavioral therapy for severe AUD. “There’s a strong dissociative effect with ketamine delivered . . . at the doses we’re delivering it,” explained Anthony Tennyson, co-founder and CEO of Awakn. During a preparative therapy session, the reasons why an individual became addicted and the addiction’s effects on others surface, and ketamine then enables a different perspective on these experiences. “Getting a different perspective and a different view on things during this dissociative effect can help some people forgive themselves and forgive other people in a much more rapid and efficient way than just talk-based therapy by itself,” Tennyson told BioSpace. Ketamine also disrupts memories, which Tennyson said are “very often triggers for relapse.” Awakn pairs its ketamine therapy with a cognitive behavioral manual that is specifically designed to help people deal with the ketamine experience. In Phase II, treatment with the regimen led to an average of 86% abstinence over the six months following treatment versus 2% prior to the trial, Awakn reported. Meanwhile, Berlin and U.S.-based atai Life Sciences is tackling opioid use disorder with ibogaine, a psychoactive compound that comes from the iboga tree and has long been used in spiritual ceremonies by indigenous people in West Central Africa. Data have shown “marked benefits” of ibogaine on opioid use disorder, including on withdrawal and persistent changes in mood and craving behavior, Srinivas Rao, chief scientific officer at atai, told BioSpace. In a review of clinical results from an open-label case series of human volunteers seeking to detoxify from opioids or cocaine, ibogaine therapy diminished withdrawal symptoms and reduced drug cravings. Atai expects to begin a Phase I/IIa trial with an intravenous form of ibogaine, IBX-210, in the second half of this year. While atai considered other molecules, including LSD, the company decided to go with ibogaine because of “compelling” aggregate data in opioid use disorder. Like Awakn, Atai is planning to deliver IBX-210 with psychological support to help participants prepare for the dosing session and integrate it into their experience afterward. ‘Not a Cure-All’ While treatments like AWKN-001 and IBX-210 are intended for people with addictive personalities, “you need to consume [ketamine] in a very significantly greater quantity and on a far more regular and ongoing basis than our treatment cycle and treatment program requires” in order for addiction to be an issue with the drug, Tennyson said. Garcia-Romeu said that substances like psilocybin are not addictive in the sense that they don’t produce withdrawal and tolerance, but acknowledged that they can create a form of psychological dependence where people seek out the drug. In general, he said, “The drugs are pretty self-limiting.” Rao added that psychedelic therapies in development are intended to be administered in a supervised medical setting to mitigate their risks. “Regardless of whatever likeability any of these compounds have, none of them are being developed for at-home therapy, so that’s an important element.” Many treatment protocols—including Awakn’s AWKN-001—are combined with talk therapy, something Todd Berrios, a Veteran of the U.S. Army Special Forces who was wounded in combat was diagnosed with both alcohol dependency and post-traumatic stress disorder, told BioSpace is critical. In August 2023, through a grant sponsored by VETS, Berrios was treated with ibogaine and 5-MeO-DMT, a psychedelic found in a wide variety of plant species and secreted by the glands of at least one toad species. Since then, “I haven’t had the urge, want or need to drink alcohol, which I thought was pretty impressive,” he said. However, he emphasized that ibogaine and 5-MeO-DMT are not a “cure-all” and that patients need to put in work. “There’s never an end game, there’s never a finish line. It’s constant work,” said Berrios, who participates in weekly men’s calls, mindful medication calls and men’s calls hosted by VETS. And the psychedelic experience is not positive for everyone. In a mixed-method study published in PLOS ONE last year, 608 participants reported extended difficulties following psychedelic experiences, including feelings of anxiety and fear, existential struggle and social disconnection. The Road Ahead While the research appears promising, psychedelic therapies still have an uphill climb. Psilocybin and LSD are experimental, Garcia-Romeu said, and they are not legal in the U.S. or “in most countries.” Rao also acknowledged that working with Schedule 1 drugs adds “a lot more paperwork,” including with importation and exportation. Additionally, Garcia-Romeu said, “We don’t really know how it works. We also are kind of in this process of understanding what types of treatments are best paired with the psychedelic because it’s not just the drug that seems to help exert these effects, but it’s almost always incorporated within some form of counseling or psychotherapy.” The other main hurdle, Garcia-Romeu said, will be accessibility. “This will likely be an expensive type of treatment, because it’s very labor intensive,” he said, noting that a course of psychedelic therapy takes around three months to complete and requires hours of psychotherapy. “So even if this becomes an approved medicine, people’s ability to access these treatments may be slow, I would say, and probably limited to people of means.” Rao also noted the stigma, or “sociological overlay,” around psychedelics. “There’s just a lot of additional baggage.” Psychedelic therapies would also require a different kind of paradigm shift, he said. “Whether it’s depression or substance use disorder, we’re really looking at intermittent therapy rather than daily therapy.” Some of the baggage could be lessened this summer if Lykos Therapeutics wins FDA approval for its midomafetamine (MDMA) capsules to treat post-traumatic stress disorder. The FDA has set a PDUFA date of August 11, 2024. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.

First participant dosed in Phase 1b trial of VLS-01 with data expected in 2H’24; Phase 2 study in TRD patients anticipated to initiate around YE’24 Beckley Psytech’s Phase 2a study of BPL-003 in TRD patients showed rapid and durable antidepressant effects; Phase 2b topline data expected in 2H’24 Compass Pathways’ Phase 2 study of COMP360 in PTSD patients demonstrated durable improvement in symptoms; Phase 3 data of COMP360 in TRD patients expected in 4Q’24 Co-Founder Florian Brand to step down as CEO as part of a planned transition by YE’24 and to be succeeded by Co-Founder and current Chief Scientific Officer Srinivas Rao, M.D., Ph.D. Cash, marketable securities, and committed term loan funding expected to fund operations into 2026 NEW YORK and BERLIN, May 15, 2024 (GLOBE NEWSWIRE) -- atai Life Sciences (NASDAQ: ATAI) (“atai” or “Company”), a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders, today announced first quarter 2024 financial results, provided corporate updates and announced a transition in its leadership. Florian Brand (“Mr. Brand”), Co-Founder and current CEO, will step down as CEO by the end of this year. Co-Founder Srinivas Rao, M.D., Ph.D. (“Dr. Rao”), currently the Chief Scientific Officer, will be promoted to Co-CEO effective June 1, 2024 and intends to assume the role of CEO by the end of the year subject to appointment as required by local law. “I co-founded atai in 2018 with the bold mission to transform mental health care, and I am immensely proud of our accomplishments and continuous progress made across our R&D programs over the last six years. To that end, looking at the recent months, we have achieved many clinical milestones, with dosing in our VLS-01 Phase 1b program well underway and encouraging Phase 2 data readouts from both BPL-003 and COMP360,” said Mr. Brand. “As I prepare to turn my focus to new entrepreneurial ventures in other areas of significant unmet medical needs, I am confident in passing the torch to my Co-Founder Srini by year-end. His exceptional leadership and deep expertise in neuropsychiatric drug development have been pivotal to our success, and I am delighted that he will be leading atai into its next phase, where his experience in late stage clinical development will be especially relevant and impactful.” Dr. Rao brings over 24 years of knowledge and experience from diverse biotechnology and pharmaceutical roles, having held the titles of Chief Scientific, Medical, or Executive Officer at companies ranging from venture-backed startups to vertically integrated, publicly traded pharmaceutical companies. “It is an honor to follow in the footsteps of my dear friend and Co-Founder, Florian. I am deeply grateful for the opportunity to continue to work with him as Co-CEOs until the end of the year and build upon our shared vision, ensuring atai’s continued success in addressing challenging mental health conditions,” said Dr. Rao. “In the near-term this year, I look forward to several data milestones, including the Phase 2b readout of BPL-003 in TRD, Phase 3 data of COMP360 in TRD and the VLS-01 Phase 1b readout.” Founder and Chairman Christian Angermayer commented: "Since its inception in 2018, atai has been at the forefront of mental health innovation, driven by a commitment to deliver ground-breaking therapies to those in need, with a special focus on psychedelic substances. Florian successfully led the company from its early days through numerous R&D, business development and financing milestones, including an IPO in 2021. Florian's leadership and execution focus have been foundational to the success of atai. We look forward to seeing the new heights he will achieve. As Florian transitions, we are deeply grateful for the enduring impact he made on our company, and while he will leave as CEO at the end of this year, he will always be part of the atai family and our success story. With his extensive experience in late stage drug development, Srini has the right pro skillset to lead atai into its next evolutionary phase.” Corporate Updates Florian Brand, Co-Founder and current CEO of atai, will assume the role of Co-CEO effective June 1, 2024 and will step down as CEO by the end of this year. Co-Founder Srinivas Rao, currently the Chief Scientific Officer of atai, will be promoted to Co-CEO effective June 1, 2024, and intends to assume the role of CEO by the end of the year subject to appointment as required by local law. Clinical Highlights VLS-01: N,N-dimethyltryptamine (DMT) for Treatment-Resistant Depression (TRD) VLS-01 is an oral transmucosal film (OTF) formulation of DMT designed to fit within the two-hour in-clinic treatment paradigm successfully established by Spravato® In March 2024, we announced the initiation of dosing in a Phase 1b study that is designed to evaluate the relative safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of an optimized OTF formulation of VLS-01, compared to intravenous (IV) DMT. Results of the Phase 1b study are anticipated in 2H 2024. The Company plans to initiate a randomized, placebo-controlled Phase 2 trial of VLS-01 in TRD patients around YE’24. BPL-003: 5-MeO-DMT for TRD as primary indication Beckley Psytech’s BPL-003 is an intranasal formulation of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) designed to fit within an approximately two hour in-clinic treatment paradigm. In March 2024, Part 1 of a Phase 2a open-label (OL) study showed that a single administration of BPL-003 resulted in rapid and durable antidepressant effects, with 45% of patients in remission three months after dosing. Acute effects resolved on average in less than two hours, and BPL-003 was found to be well-tolerated, with no serious adverse events reported. In April 2024, Part 2 of the Phase 2a OL study initiated to investigate BPL-003 as an adjunctive therapy to Selective Serotonin Reuptake Inhibitors in TRD patients. A randomized, controlled Phase 2b study of BPL-003 in TRD patients is underway with topline data expected in 2H 2024. COMP360: Psilocybin Therapy for TRD as primary indication Compass Pathways’ COMP360 is an oral formulation of synthetic psilocybin that is currently being evaluated in multiple clinical studies. In May 2024, results from an OL Phase 2 study in 22 patients with PTSD showed that COMP360 met its primary safety endpoint and was well tolerated, with no serious adverse events. COMP360 demonstrated a rapid and durable improvement in PTSD symptoms. Week 4 and 12 reductions in the CAPS-5 total score of 29.9 and 29.5, respectively, were observed. The response rate, as defined by patients experiencing a ≥ 15-point improvement on CAPS-5 score, was 81.8% at week 4 and 77.3% at week 12. The remission rate, as defined by CAPS-5 total score of ≤ 20, was 63.6% at week 4 and 54.5% at week 12. The Phase 3 program of COMP360 in TRD patients is composed of two pivotal trials, each with a long-term follow-up component. Pivotal Trial 1 (COMP005) topline data is expected in the fourth quarter of 2024 and Pivotal Trial 2 (COMP006) topline data is anticipated mid-2025. Upcoming R&D Catalysts 1H’24 ELE-101 MDD Phase 1/2a initial data 2H’24 VLS-01 Phase 1b topline data BPL-003 AUD Phase 2a OL data (mid’24) COMP360 TRD Phase 3 Pivotal Trial 1 topline data BPL-003 TRD Phase 2b data IBX-210 OUD Phase 1/2a initiation VLS-01 TRD Phase 2 initiation (around YE’24) 2025 RL-007 CIAS Phase 2b topline data (mid’25) COMP360 TRD Phase 3 Pivotal Trial 2 topline data (mid’25) Consolidated Financial Results Cash, cash equivalents, and short-term investments: As of March 31, 2024, the Company had cash, cash equivalents, restricted cash and short-term investments of $121.3 million compared to $154.2 million as of December 31, 2023. The decrease of $32.9 million was primarily driven by $22.6 million net cash used in operating activities and $10 million for the Beckley Psytech investment. The Company expects its cash, marketable securities and committed term loan facility with Hercules Capital, Inc. to be sufficient to fund operations into 2026. Research and development (R&D) expenses: R&D expenses were $11.5 million for the three months ended March 31, 2024, as compared to $19.3 million for the same prior year period. The year-over-year decrease of $7.8 million was primarily attributable to a decrease of $5.1 million in program-specific expenses and $2.6 million in R&D personnel. Within program-specific expenses, the decrease was primarily driven by more clinical trials, discovery expenses and manufacturing costs in prior year. During the quarter, the Company allocated capital resources to invest in the R&D activities of its Beckley Psytech strategic investment. The Company is anticipating R&D spend to increase as its R&D programs progress into later stage clinical trials. General and administrative (G&A) expenses: G&A expenses for the three months ended March 31, 2024 were $12.6 million as compared to $14.0 million in the same prior year period. The year-over-year decrease of $1.4 million was primarily attributable to $2.6 million decrease in personnel related expenses, $0.7 million net decrease of professional services and other administrative expenses, partially offset by a $1.9 million increase related to a prior year non-income tax refund. The Company is actively controlling G&A spend. The Company expects the reduction in G&A spend over prior years to continue. Net loss: Net loss attributable to stockholders for the three months ended March 31, 2024, was $26.7 million as compared to $33.1 million for the three months ended March 31, 2023. atai Life Sciences atai is a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders and was founded as a response to the significant unmet need and lack of innovation in the mental health treatment landscape. atai is dedicated to efficiently developing innovative therapeutics to treat depression, anxiety, addiction, and other mental health disorders. By pooling resources and best practices, atai aims to responsibly accelerate the development of new medicines to achieve clinically meaningful and sustained behavioral change in mental health patients. atai's vision is to heal mental health disorders so that everyone, everywhere can live a more fulfilled life. For more information, please visit . Forward-looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “anticipate,” “initiate,” “could,” “would,” “project,” “plan,” “potentially,” “preliminary,” “likely,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements include express or implied statements relating to, among other things: our business strategy and plans; transition plans for our CEO and Co-CEO; the potential, success, cost and timing of development of our product candidates, including the progress of preclinical and clinical trials and related milestones; expectations regarding our strategic investment in Beckley Psytech; expectations regarding our cash runway; and the plans and objectives of management for future operations, research and development and capital expenditures. Forward-looking statements are neither promises nor guarantees, but involve known and unknown risks and uncertainties that could cause actual results to differ materially from those projected, including, without limitation, the important factors described in the section titled “Risk Factors” in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (“SEC”), as such factors may be updated from time to time in atai's other filings with the SEC. atai disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by applicable law. Contact Information Investor Contact: IR@atai.life Media Contact: PR@atai.life ATAI LIFE SCIENCES N.V. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Amounts in thousands, except share and per share amounts) Three Months Ended March 31, 2024 2023 (unaudited) License revenue $ — $ 37 Operating expenses: Research and development 11,530 19,281 General and administrative 12,555 13,970 Total operating expenses 24,085 33,251 Loss from operations (24,085 ) (33,214 ) Other income (expense), net (1,596 ) 58 Loss before income taxes (25,681 ) (33,156 ) Benefit from (provision for) income taxes 4 (165 ) Losses from investments in equity method investees, net of tax (1,701 ) (1,033 ) Net loss (27,378 ) (34,354 ) Net loss attributable to noncontrolling interests (665 ) (1,219 ) Net loss attributable to ATAI Life Sciences N.V. stockholders $ (26,713 ) $ (33,135 ) Net loss per share attributable to ATAI Life Sciences N.V. stockholders — basic and diluted $ (0.17 ) $ (0.21 ) Weighted average common shares outstanding attributable to ATAI Life Sciences N.V. stockholders — basic and diluted 158,891,067 155,792,490 ATAI LIFE SCIENCES N.V. CONDENSED CONSOLIDATED BALANCE SHEET (Amounts in thousands) (unaudited) March 31, December 31, 2024 2023 Assets Cash and cash equivalents $ 18,867 $ 45,034 Short term restricted cash for other investments 5,000 - Securities carried at fair value 87,379 109,223 Committed Investment Funds - 25,000 Prepaid expenses and other current assets 5,732 5,830 Short term notes receivable - related party, net 522 505 Long term restricted cash for other investments 10,000 - Property and equipment, net 920 981 Operating lease right-of-use asset, net 1,115 1,223 Other investments held at fair value 90,205 89,825 Other investments 32,807 1,838 Long term notes receivable - related parties, net 98 97 Convertible notes receivable - related party 13,902 11,202 Other assets 2,574 2,720 Total assets $ 269,121 $ 293,478 Liabilities and Stockholders' Equity Accounts payable 3,843 4,589 Accrued liabilities 10,926 15,256 Current portion of lease liability 244 275 Contingent consideration liability - related parties 607 620 Contingent consideration liability 1,406 1,637 Noncurrent portion of lease liability 907 990 Convertible promissory notes - related parties 417 164 Convertible promissory notes and derivative liability 4,099 2,666 Long term debt, net 15,140 15,047 Other liabilities 8,275 7,918 Total stockholders' equity attributable to ATAI Life Sciences N.V. stockholders 222,544 242,962 Noncontrolling interests 713 1,354 Total liabilities and stockholders' equity 269,121 293,478