February 24, 2025

DeFloria plans to initiate a Phase 2 clinical trial by mid-year 2025

LITTLETON, Colo., Feb. 24, 2025 /PRNewswire/ -- DeFloria, Inc., a collaboration between Ajna BioSciences PBC and Charlotte's Web Holdings, Inc. (TSX: CWEB, OTCQX: CWBHF), announced that the U.S. Food and Drug Administration (FDA) has completed its review of the Investigational New Drug (IND) application for AJA001, an orally delivered, multi-cannabinoid botanical drug, concluding that the Company may proceed with its planned Phase 2 clinical trial. DeFloria is developing AJA001 as a treatment for symptoms of autism spectrum disorder (ASD) and plans to initiate the Phase 2 study by mid-year 2025.

With as many as 1 in 36 children diagnosed, ASD represents a growing and underserved market valued at nearly $4 billion in the U.S. with a greater than 4% compounded annual growth rate (CAGR). Safe and effective treatment options are severely limited for the autism community, with only two approved treatments - atypical antipsychotics that exhibit frequent adverse side effects, poor tolerance, and a lack of compliance from patients.

"IND submission for AJA001 and the initiation of the Phase 2 study in the US mark a historic moment in our mission to develop a systemically absorbed botanical drug therapy that meets guidelines established by the FDA for advanced clinical testing," said Jared Stanley, CEO of DeFloria. "DeFloria is committed to supporting the ASD community and developing AJA001 to treat the behavioral symptoms associated with ASD with a drug that is designed to provide broad therapeutic efficacy."

AJA001 was developed by DeFloria, Ajna BioSciences and Charlotte's Web to leverage a decade of Charlotte's Web's observational data, research, and innovative cultivation processes that are the foundation of the proprietary hemp genetics of AJA001. The unique collaboration also brings compliance with current good manufacturing practices (cGMP) and FDA quality requirements to advance a pharmaceutical botanical drug through development and ultimately to support a registrational review and approval process. 

"It is exciting to see AJA001 advance through the botanical drug pathway following the guidance established by the FDA," stated Jinhui Dou, Ph.D., former FDA expert pharmacologist and botanical review team lead. "As the first orally ingested botanical drug designed to meet cGMP and quality standards, AJA001 is setting the bar for future pharmaceuticals in this class."

The Phase 2 clinical trial is designed as an open-label, 12-week study to investigate AJA001 as a potential treatment for the behavioral symptoms associated with ASD. The study will enroll 60 adolescent and young adult patients (ages 13-29 years old). The primary goal of the Phase 2 study will be to establish a titration regimen and efficacy signals to inform dosing levels for Phase 3 studies.

"There is strong data supporting the potential efficacy of cannabinoids to treat autism spectrum disorder, offering what we hope will be a safer and more effective therapy than what is currently available," stated Orrin Devinsky, MD and Chief Medical Advisor."DeFloria is at the forefront of advancing a promising drug for this indication through the FDA's rigorous assessment process to potentially help millions affected by autism spectrum disorder." 

In addition to the US Phase 2 open-label IND study, DeFloria also plans to initiate a Phase 2 open-label pediatric study of AJA001 in Australia in 2025.

"For more than 15 years, my family and our team have been laying the foundation for this botanical drug," said Joel Stanley, CEO, Ajna BioSciences and Chairman of the Board, DeFloria. "Charlotte Figi's story, shared by Dr. Sanjay Gupta on CNN, put the benefits of cannabinoids on the world's radar and sparked a movement. Now, with this Phase 2 milestone, we're one step closer to delivering a potential treatment option for autism spectrum disorder, a condition for which few effective therapies exist despite impacting millions worldwide."

About ASDApproximately 1 in 36 children may have autism spectrum disorder (ASD) (Maenner et al 2023). ASD is characterized by core deficits in (1) social communication, (2) impaired reciprocal social interactions, and (3) restricted, repetitive and stereotyped patterns of behaviors or interests. Irritability, impulsivity, and "temper tantrums" are common symptoms and contribute to high caregiver burden (Lecavalier et al 2006).

About AJA001AJA001 is a botanical drug consisting of full spectrum hemp extract (FSHE) derived from Cannabis sativa L proprietary CW1AS1 hemp cultivar. The primary cannabinoid is cannabidiol (CBD) and includes other cannabinoids that are expected to have activity. As an innovative multi-cannabinoid botanical drug, AJA001 may provide broad therapeutic efficacy with potential therapeutic applications across various medical conditions due to its varied mechanisms of action. 

About DeFloriaDeFloria, Inc. a collaboration between Charlotte's Web, Inc., AJNA BioSciences PBC, and British American Tobacco PLC (BAT), is on a mission to address crucial healthcare needs through groundbreaking innovations from multi-compound drugs originating in nature. DeFloria merges the experience of its partners with other drug development experts, for a combined century of experience in regulatory, research, and quality-controlled standardized manufacturing. DeFloria's ambitious endeavor aims to secure FDA approval for a novel botanical drug developed from Charlotte's Web proprietary hemp genetics that targets autism spectrum disorder (ASD).

About Ajna BioSciences
Ajna BioSciences PBC is a botanical drug development company based in Denver, Colorado, focused on natural pharmaceuticals for Central Nervous System disorders. With specialized laboratory infrastructure and industry-leading Chemistry, Manufacturing, and Controls (CMC) capabilities, Ajna accelerates the development of FDA-approved botanical medicines. Ajna leads CMC in the partnership, regulatory filings, commercialization strategies, and interfaces with DeFloria's experts to guide the clinical trial programs.

About Charlotte's Web
Charlotte's Web Holdings, Inc., a Certified B Corporation and the market leader in hemp wellness products, pioneered the CBD industry with its groundbreaking full-spectrum hemp extracts. Founded by the seven Stanley Brothers, Charlotte's Web set the standard for quality and efficacy in plant-based health solutions, earning global recognition as the world's most trusted hemp extract. As a partner in DeFloria, Charlotte's Web contributes years of intellectual property and over $50 million in GMP manufacturing infrastructure, ensuring scalable production for clinical trials and future market supply.

Cautionary Note of Forward-Looking Statement

This press release may contain forward-looking statements. Forward-looking statements include all statements that do not relate solely to historical or current facts and can be identified by the use of words such as "may," "will," "expect," "project," "estimate," "anticipate," "plan," "believe," "potential," "should," "continue" or the negative versions of those words or other comparable words. Forward-looking statements are not guarantees of future actions or performance. These forward-looking statements, include those related to drug development outcomes, and are based on information currently available to the Company and its current plans or expectations and are subject to a number of uncertainties and risks that could significantly affect current plans. The Company is under no obligation to, and expressly disclaims any such obligation to, update or alter its forward-looking statements, whether as a result of new information, future events or otherwise.

Investor Contact:Tiberend Strategic Advisors, Inc.
Jon Nugent
(205) 566-3026
jnugent@tiberend.com

Media Contact:Tiberend Strategic Advisors, Inc.
Casey McDonald
(646) 577-8520
cmcdonald@tiberend.com

References:

Maenner MJ, Warren Z, Williams AR, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020. MMWR Surveill Summ 2023;72(No. SS-2):1–14.

Lecavalier L, Leone S, Wiltz J. The impact of behaviour problems on caregiver stress in young people with autism spectrum disorders. J Intellect Disabil Res. 2006;50(Pt 3):172-83.

SOURCE DeFloria, LLC

December 12, 2024

Single Ascending and Multiple Ascending Dose Trial Demonstrated AJA001 to be Safe and Well-tolerated, with Formulation Optimized for ASD

Presentation at the 63rd Annual Meeting of the American College of Neuropsychopharmacology

LITTLETON, Colo., Dec. 12, 2024 /PRNewswire/ -- DeFloria, a joint venture between Ajna BioSciences and Charlotte's Web (TSX: CWEB, OTCQX: CWBHF), reported positive results from a Phase 1 single ascending and multiple ascending dose trial of AJA001 in development for the treatment of symptoms of autism spectrum disorder (ASD) in a poster presentation at the 63rd Annual Meeting of the American College of Neuropsychopharmacology in Phoenix, Arizona.  AJA001 is an orally delivered, multi-cannabinoid botanical drug product (BDP) designed to provide a broad therapeutic effect.

In a poster entitled, "A Single and Multiple Ascending Dose and Food Effect Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AJA001, a Full-Spectrum Hemp-Derived Botanical Drug for Autism Spectrum Disorder, " Marcel O. Bonn-Miller, Ph.D., Chief Scientific Officer at Charlotte's Web and Board Member at DeFloria, presented the results from the recently completed Phase 1 randomized, double-blind, placebo-controlled trial that evaluated the tolerability and pharmacokinetic (PK) / pharmacodynamic (PD) profile of several dose levels of AJA001 in 70 healthy volunteers ranging from 19 to 55 years.

Results demonstrated that AJA001 was well-tolerated at doses up to 680 mg per day administered as a single dose and up to 660 mg per day administered twice a day. In both the single and multiple ascending dose portions of the trial, AJA001 displayed dose-proportional PK for CBD and THC that matched or exceeded the plasma concentrations of the comparable cannabinoid therapeutics dronabinol, nabiximols, and Epidiolex®. PK data following multiple dose administration of AJA001 showed minimal accumulation of CBD or THC after 7 days.

AJA001's PD effects were shown to be dose-dependent and correlated with peak plasma concentrations of THC and its active metabolite 11-OH-THC after administration of single doses. An analysis of participant responses on the Drug Effects Questionnaire (DEQ) demonstrated that the magnitude and time course of AJA001's subjective drug effects were moderate and transient in nature. 

The safety, PK, and PD findings support doses from 100 mg to 660 mg  of AJA001 per day for Phase 2 trials in children, adolescents, and adults with ASD. This is equivalent to an upper limit of 395 mg CBD and 15 mg THC per day. The most common treatment emergent adverse events in the AJA001 treated groups were somnolence, anxiety, dizziness, and headache. One serious adverse event was reported by a participant receiving 906.4 mg of AJA001 who reported anxiety that resolved by the next day with no sequalae.

A copy of the poster is available on the DeFloria website at http://defloria.bio. 

"We are extremely encouraged by these results from our Phase 1 single and multiple ascending dose trial, which demonstrate that AJA001 is well-tolerated across a range of doses and provides a favorable pharmacokinetic profile for both cannabidiol and tetrahydrocannabinol," said Dr. Bonn-Miller.  "Importantly, the results from this trial inform the doses to be evaluated in upcoming Phase 2 clinical trials of AJA001 in children, adolescents, and adults with ASD."

 "We are excited to present this important data and look forward to initiating two Phase 2 trials of AJA001 in ASD in the second quarter of 2025," said Jared Stanley, CEO of DeFloria.  "Despite its prevalence, ASD remains a difficult condition to treat.  Moreover, currently available treatments for ASD are not well tolerated, making patient compliance a challenge.  DeFloria is committed to supporting the ASD community and developing AJA001 to treat the behavioral symptoms associated with ASD with a drug product that is designed to provide broad therapeutic efficacy."   

About ASD

Approximately 1 in 36 children may have ASD (Maenner et al 2023). ASD is characterized by core deficits in (1) social communication, (2) impaired reciprocal social interactions, and (3) restricted, repetitive and stereotyped patterns of behaviors or interests. Irritability, impulsivity, and "temper tantrums" are common symptoms and contribute to high caregiver burden (Lecavalier et al 2006).

About AJA-001

AJA001 Oral Solution is a botanical drug product (BDP) containing full spectrum hemp extract (FSHE) botanical drug substance (BDS) derived from Cannabis sativa L proprietary CW1AS1 hemp cultivar.  The primary cannabinoid is cannabidiol (CBD).  As an innovative multi-cannabinoid formulation, it may provide broad therapeutic efficacy. Its full-spectrum composition has potential therapeutic applications across various medical conditions due to its varied mechanisms of action. 

About DeFloria

DeFloria LLC, a collaboration between Charlotte's Web, Inc., AJNA BioSciences PBC, and British American Tobacco PLC (BAT), is on a mission to address crucial healthcare needs through groundbreaking innovations from multi-compound drugs originating in nature. With a combined century of experience in regulatory, research, and quality-controlled standardized manufacturing, DeFloria's ambitious endeavor aims to secure FDA approval for a novel cutting-edge botanical drug developed from Charlotte's Web proprietary hemp genetics that targets a neurological condition identified by the DeFloria leadership and research teams.

Cautionary Note of Forward-Looking Statement

This news release contains "forward-looking statements" within the meaning of the United States Private Securities Litigation Reform Act of 1995. Often, but not always, forward-looking statements can be identified by the use of words such as "plans", "expects" or "does not expect", "is expected", "estimates", "intends", "anticipates" or "does not anticipate", or "believes", or variations of such words and phrases or state that certain actions, events or results "may", "could", "would", "might" or "will" be taken, occur or be achieved. Forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of DeFloria, LLC to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements contained in this news release. Examples of such statements and uncertainties include statements with respect to future dose trial results, therapeutic efficacy, or approvals of AJA001 Oral Solution.

Risks, uncertainties and other factors involved with forward-looking statements could cause actual events, results, performance, prospects and opportunities to differ materially from those expressed or implied by such forward-looking statements, including negative outcomes in future dose trials, therapeutic efficacy, or delays in approvals of AJA001 Oral Solution.

In respect of the forward-looking statements, DeFloria, LLC has provided such statements in reliance on certain assumptions that it believes are reasonable at this time.  Although DeFloria, LLC and its collaborators and partners believe that the assumptions and factors used in preparing the forward-looking statements in this news release are reasonable, undue reliance should not be placed on such information or statements and no assurance can be given that such events will occur in the disclosed time frames or at all. Should one or more of the foregoing risks or uncertainties materialize, or should assumptions underlying the forward-looking statements prove incorrect, actual results may vary materially from those described herein as intended, planned, anticipated, believed, estimated or expected. Although DeFloria, LLC has attempted to identify important risks, uncertainties and factors which could cause actual results to differ materially, there may be others that cause results not to be as anticipated, estimated or intended. The forward-looking statements included in this news release are made as of the date of this news release and DeFloria, LLCs does not undertake any obligation to publicly update such forward-looking statements to reflect new information, subsequent events or otherwise unless required by applicable securities laws.

Investor/Media Contact

Tiberend Strategic Advisors, Inc.
Casey McDonald
(646) 577-8520
cmcdonald@tiberend.com  

References:

Maenner MJ, Warren Z, Williams AR, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020. MMWR Surveill Summ 2023;72(No. SS-2):1–14.  

Lecavalier L, Leone S, Wiltz J. The impact of behaviour problems on caregiver stress in young people with autism spectrum disorders. J Intellect Disabil Res. 2006;50(Pt 3):172-83. 

SOURCE DeFloria, LLC

December 13, 2023

Phase 1 Results to Inform Phase 2 studies in 1H24

DENVER, Dec. 13, 2023 /PRNewswire/ - (TSX: CWEB) (OTCQX: CWBHF), Charlotte's Web Holdings, Inc. ("Charlotte's Web," "CW" or the "Company"), the market leader in full-spectrum hemp extract wellness products, and AJNA BioSciences PBC ("AJNA"), a botanical drug development company focused on mental health and neurological disorders, announced today that DeFloria LLC ("DeFloria") commenced its First-in-Human Phase 1 clinical trial for AJA001, a full-spectrum botanical drug.

Dr. Orrin Devinsky Ph.D., the Chief Medical Advisor at AJNA Biosciences stated, "Our phase 1 entrance marks a critical milestone in AJA001's clinical timeline and advances a full-spectrum cannabinoid formulation into rigorous clinical trials that are essential to advance medical science. We are proud of our team's hard work to reach this point, and I am excited to help develop the Phase 2 program for this new drug."

AJA001's initial research is dedicated to the examination of the safety, tolerability, pharmacokinetics, and pharmacodynamics in fasted and fed healthy participants of a full spectrum hemp oil extracted from one of Charlotte's Web's patented hemp cultivars ("AJA001"). The study includes single ascending dose and a seven-day multiple ascending dose administration phases. The study is expected to involve around 64 participants. The first cohort was dosed in early September and DeFloria expects preliminary results in the first quarter of 2024. The study is being conducted with Nucleus Networks in Brisbane, Australia.

"The initiation of the AJA001 clinical program serves as an important milestone for DeFloria. Data from this study will help us better understand the safety profile of AJA001 and position us to move into Phase 2 studies with greater dosing accuracy," remarked Dr. Marcel Bonn-Miller Ph.D., Chief Scientific Officer at Charlotte's Web.

AJA001, an investigational full-spectrum cannabinoid drug, leverages Charlotte's Web's proprietary hemp genetics. As an innovative multi-cannabinoid formulation, it may provide a more complete therapeutic action relative to single-molecule alternatives. Its full-spectrum composition has potential therapeutic applications across various medical conditions due to its varied mechanisms of action. 

"This achievement shows the commitment and excellence of our top-tier team. At DeFloria, we have united the early leaders in CBD with the finest minds in clinical and biotechnological research. This milestone is a big one for early adopters in botanical drug development, and especially for those of us that have known cannabinoid therapies would become very important in modern medicine. As we approach Phase 2 efficacy trials in the new year, DeFloria is establishing itself as a key player and leader in the new field of botanical drugs," noted Joel Stanley, Co-Founder of AJNA BioSciences."

Following completion of this Phase 1 study, DeFloria plans to submit an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) to commence the Phase 2 clinical program for AJA001. AJA001 is being developed through the FDA's botanical drug pathway, which serves as a specialized regulatory framework, streamlining the development and approval of pharmaceutical products derived from plants or plant-based substances, acknowledging their unique properties. This approach aims to strike a balance between harnessing existing knowledge about botanicals and ensuring that these products adhere to the same stringent quality, safety, and efficacy standards as conventional pharmaceuticals.

About DeFloria LLCDeFloria LLC, a collaboration between Charlotte's Web, Inc., AJNA BioSciences PBC, and British American Tobacco PLC (BAT), is on a mission to address crucial healthcare needs through groundbreaking innovations from multi-compound drugs originating in nature. With a combined century of experience in regulatory, research, and quality-controlled standardized manufacturing, DeFloria's ambitious endeavor aims to secure FDA approval for a novel cutting-edge botanical drug developed from Charlotte's Web proprietary hemp genetics that targets a neurological condition identified by the DeFloria leadership and research teams. Visit www.defloria.bio

About AJNA BioSciences PBCAJNA BioSciences PBC is a botanical drug development company based in Denver, Colorado, focused on natural pharmaceuticals that address mental health and neurological disorders. The Company's strategy encompasses selecting plant and fungi species with a well-established history of therapeutic use, which streamlines drug discovery, mitigates late-stage clinical trial risk, to advance unprecedented medicinal breakthroughs. AJNA's unique platform is designed for rapid development of investigational new drugs by combining specialized laboratory infrastructure and CMC capabilities with top-tier clinical and regulatory expertise. AJNA's commercialization strategy is flexibly designed for co-development partnerships, IP licensing, and vertically integrated drug products in a broad range of botanical species and clinical indications. As a public benefit corporation, AJNA's business model maximizes profitability and sustainability for both people and the planet. Visit www.AjnaBiosciences.com

About Charlotte's Web Holdings, Inc. Charlotte's Web Holdings, Inc., a Certified B Corporation headquartered in Louisville, Colorado, is the market leader in innovative hemp extract wellness products under a family of brands that includes Charlotte's Web™, ReCreate™, CBD Medic™, and CBD Clinic™. Charlotte's Web whole-plant CBD extracts come in full-spectrum and broad-spectrum options, including ReCreate™ by Charlotte's Web, broad-spectrum CBD certified NSF for Sport®. ReCreate is the official CBD of Major League Baseball©, Angel City Football Club and the Premier Lacrosse League. Charlotte's Web branded premium quality products start with proprietary hemp genetics that are North American farm-grown using organic and regenerative cultivation practices. The Company's hemp extracts have naturally occurring botanical compounds including cannabidiol ("CBD"), CBC, CBG, terpenes, flavonoids, and other beneficial compounds. Charlotte's Web product categories include CBD oil tinctures (liquid products) CBD gummies (sleep, calming, exercise recovery, immunity), CBD capsules, CBD topical creams and lotions, as well as CBD pet products for dogs. Through its substantially vertically integrated business model, Charlotte's Web maintains stringent control over product quality and consistency with analytic testing from soil to shelf for quality assurance. Charlotte's Web products are distributed to retailers and health care practitioners throughout the U.S.A, and online through the Company's website at www.charlottesweb.com.

© Major League Baseball trademarks and copyrights are used with permission of Major League Baseball. Visit MLB.com.

Forward-Looking Information

Certain information provided herein constitutes forward-looking statements or information (collectively, "forward-looking statements") within the meaning of applicable securities laws. Forward-looking statements are typically identified by words such as "may", "will", "should", "could", "anticipate", "expect", "project", "estimate", "forecast", "plan", "intend", "target", "believe" and similar words suggesting future outcomes or statements regarding an outlook. Forward-looking statements are not guarantees of future performance and readers are cautioned against placing undue reliance on forward-looking statements. By their nature, these statements involve a variety of assumptions, known and unknown risks and uncertainties, and other factors which may cause actual results, levels of activity, and achievements to differ materially from those expressed or implied by such statements. The forward-looking statements contained in this press release are based on certain assumptions and analysis by management of the Company in light of its experience and perception of historical trends, current conditions and expected future development and other factors that it believes are appropriate and reasonable. Specifically, this news release contains forward-looking statements relating to, among others, the ability of DeFloria to achieve its purpose, including obtaining FDA approval of a new CBD-based botanical drug.

The material factors and assumptions used to develop the forward-looking statements herein include, but are not limited to: regulatory regime change and including but not limited to those risks and uncertainties discussed under the heading "Risk Factors" in the Company's Annual Report on Form 10-K for the year ending December 31, 2022 and other risk factors contained in other filings with the Securities and Exchange Commission available on www.sec.gov and filings with Canadian securities regulatory authorities available on www.sedarplus.ca. The impact of any one risk, uncertainty, or factor on a particular forward-looking statement is not determinable with certainty as these are interdependent, and the Company's future course of action depends on management's assessment of all information available at the relevant time.

Any forward-looking statement in this press release is based only on information currently available to the Company and speaks only as of the date on which it is made. Except as required by applicable law, the Company assumes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. All forward-looking statements, whether written or oral, attributable to the Company or persons acting on the Company's behalf, are expressly qualified in their entirety by these cautionary statements.

SOURCE Charlotte's Web Holdings, Inc.