UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 6-K
Report of Foreign Private Issuer
Pursuant to Rule 13a-16 or 15d-16
under the Securities Exchange Act of 1934
For the month of June, 2022
Commission File Number: 001-41106
Incannex Healthcare Limited
(Exact name of Registrant as specified in its charter)
not applicable
(Translation of Registrant’s name into English)
Australia
(Jurisdiction of incorporation or organization)
Joel Latham
Chief Executive Officer and Managing Director
Level 39, Rialto
South Tower
525 Collins Street
Melbourne 3000
Australia
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover Form 20-F or Form 40-F:
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):
Yes ☐ No ☒
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7):
Yes ☐ No ☒
INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K
On June 03, 2022, Incannex Healthcare Limited filed with the Australian Securities Exchange an announcement captioned “Positive final results from IHL-42X phase 2 trial”, a copy of which announcement is attached to this Form 6-K as Exhibit 99.1.
On June 03, 2022, Incannex Healthcare Limited filed with the Australian Securities Exchange an announcement captioned “IHL-42X phase 2 clinical trial presentation”, a copy of which announcement is attached to this Form 6-K as Exhibit 99.2.
1
Signatures
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
| Incannex Healthcare Limited | ||
| Date: June 03, 2022 | By: | /s/ Joel Latham |
| Name: | Joel Latham | |
| Title: | Chief Executive Officer and Managing Director | |
2
INDEX TO EXHIBITS
| Exhibit No. | ||
| 99.1 | ASX Announcement, dated June 03, 2022 – Positive final results from IHL-42X phase 2 trial | |
| 99.2 | ASX Announcement, dated June 03, 2022 – IHL-42X phase 2 clinical trial presentation |
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Exhibit 99.1
 |
Date: June 03, 2022 Public Announcement (NASDAQ: IXHL) (ASX: IHL) |
Incannex announces positive results from phase
2 clinical trial investigating
the effect of IHL-42X for treatment of obstructive sleep apnoea
Highlights:
| ● | IHL-42X reduced primary endpoint apnoea hypopnea index relative to baseline at all three doses that were assessed |
| ● | Low dose IHL-42X exhibited superior safety and efficacy metrics to mid and high doses |
| ● | Low dose IHL-42X reduced AHI by an average of 50.7% compared to baseline with 25% of participants experiencing a reduction in the apnoea hypopnea index of greater that 80% |
| ● | Oxygen desaturation index was reduced by 59.7% relative to baseline while taking low dose IHL-42X, improving sleep quality and reducing cardiovascular stress |
| ● | In low dose IHL-42X samples, THC concentrations in blood were well below the limits for impaired driving the morning after dose administration |
| ● | IHL-42X was well tolerated – low dose IHL-42X was observed to have a lower number of total treatment emergent adverse events than placebo |
| ● | Low dose IHL-42X reduced AHI substantially more effectively than is reported for the component active pharmaceutical ingredients, dronabinol and acetazolamide, as unregistered monotherapies. |
Melbourne, Australia, June 3, 2022 – Incannex Healthcare Limited (Nasdaq: IXHL) (ASX: IHL), (‘Incannex’ or the ‘Company’) a clinical-stage pharmaceutical company developing unique medicinal cannabinoid pharmaceutical products and psychedelic medicine therapies for unmet medical needs, is pleased to announce that it has completed analysis of data from the phase 2 proof-of-concept clinical trial investigating IHL-42X for treatment of obstructive sleep apnoea (‘OSA’). IHL-42X reduced apnoea hypopnoea index (‘AHI’), improved patient reported sleep quality and was well tolerated.
The clinical trial assessed three doses of IHL-42X at reducing the AHI in patients who suffered from OSA. Data was also collected for other aspects of sleep quality, THC clearance and safety. Trial participants received each of the three doses of IHL-42X and placebo across four seven-day treatment periods, separated by one week washout periods. At the end of each treatment period, they attended the clinic for an overnight sleep study where AHI was determined, along with other measures of sleep quality, quality of life and drug safety.
The study was conducted at the University of Western Australia Centre for Sleep Science and The Alfred Hospital. A total of eleven participants were recruited to the study and ten participants completed treatment periods. The crossover design of the study permitted Incannex to generate high quality data with a reduced participant number compared to a conventional parallel arm study. Each participant serves as their own internal control and inter-participant variation is eliminated. Data analysis was completed by Novotech, the contract research organisation responsible for management of the study, as well as the Incannex scientific research team, led by Chief Scientific Officer Dr Mark Bleackley. The findings of the clinical trial are presented below.
Incannex Healthcare Limited (ABN: 93 096 635 246)
Level 39, Rialto South Tower, 525 Collins Street, Melbourne VIC 3000
P: +61 409 840 786
Page 1 | 6
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Date: June 03, 2022 Public Announcement (NASDAQ: IXHL) (ASX: IHL) |
Effect of IHL-42X on apnoea hypopnoea index (AHI)
AHI is a measure of the number of times per hour a subject’s airway is blocked (apnoea) or partially blocked (hypopnoea). It is the main criteria used to diagnose and monitor OSA. AHI data was collected during overnight polysomnography on night seven of the treatment periods.
| ● | All doses of IHL-42X reduced AHI in patients with sleep apnoea compared to baseline (Table 1). This reduction was substantially greater than observed for placebo. | |
| ● | At the group level the difference relative to baseline with low dose and medium dose was statistically significant (p<0.05) | |
| ● | When comparing directly to baseline within subjects the difference in AHI compared to baseline between all three doses and placebo was statistically significant (p<0.001) (Table 2) | |
| ● | Low dose IHL-42X reduced AHI by >50% relative to baseline in 62.5% of subjects and by >80% in 25% of subjects (Table 2). | |
| ● | Low dose IHL-42X reduced AHI to the greatest extent at both the group level and when comparing the within subject reduction relative to baseline | |
| ● | Low dose IHL-42X reduced AHI to a greater extent than predicted based on published data for dronabinol and acetazolamide alone (Table 3). |
The reduction in AHI observed during IHL-42X treatment periods means that when treated with Incannex’s proprietary drug, subject’s breathing was interrupted less frequently during sleep. This supports Incannex’s hypothesis that IHL-42X is an effective treatment for OSA. The observation that low dose IHL-42X was the most effective at reducing AHI is encouraging for the development of IHL-42X as a pharmaceutical as a lower dose will reduce risk of side effects and the cost of goods.
Furthermore, greater reduction in AHI with low dose IHL-42X compared to dronabinol and acetazolamide at equivalent doses supports Incannex’s hypothesis that the two drugs are acting synergistically to reduce AHI and provides confidence that IHL-42X will meet the FDA’s combination rule where both APIs must contribute to the therapeutic effect of a fixed dose combination product.
Table 1. Average AHI data for baseline and each treatment period
| Baseline | Placebo | Low | Medium | High | ||||||||||||||||
| Average AHI | 42.84 | 40.08 | 21.13 | 22.22 | 27.78 | |||||||||||||||
| Standard deviation | 20.33 | 18.16 | 15.92 | 15.52 | 17.61 | |||||||||||||||
| % Reduction relative to baseline | N/A | 6.44 | 50.69 | 48.13 | 35.16 | |||||||||||||||
| p value compared to baseline | N/A | 0.76 | 0.029 | 0.031 | 0.12 | |||||||||||||||
Incannex Healthcare Limited (ABN: 93 096 635 246)
Level 39, Rialto South Tower, 525 Collins Street, Melbourne VIC 3000
P: +61 409 840 786
Page 2 | 6
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Date: June 03, 2022 Public Announcement (NASDAQ: IXHL) (ASX: IHL) |
Table 2. Change in AHI from baseline within subject (least square mean)
| Average change in AHI from baseline | p-value relative to placebo (Bonferroni adjusted) | Proportion of subjects with AHI reduction >50% relative to baseline (%) | Proportion of subjects with AHI reduction >80% relative to baseline (%) | |||||||||||||
| Placebo | 1.95 | N/A | 10 | 0 | ||||||||||||
| Low | 17.51 | <0.001 | 62.5 | 25 | ||||||||||||
| Medium | 14.86 | <0.001 | 33.3 | 11.1 | ||||||||||||
| High | 16.18 | <0.001 | 22.2 | 11.1 | ||||||||||||
Table 3. Comparison of reduction in AHI relative to baseline with low dose IHL-42X and the predicted reduction with component drugs as monotherapies at equivalent doses based on reported data.
| Reduction in AHI compared to baseline (%) | ||||
| 2.5 mg dronabinol (1) | 23.4 | |||
| 125 mg acetazolamide (2) | 23.4 | |||
| Low dose IHL-42X | 50.7 | |||
Effect of IHL-42X on oxygen desaturation index (ODI)
Oxygen desaturation index (‘ODI’) is the number of episodes of oxygen desaturation per hour of sleep, with oxygen desaturation defined as a decrease in blood oxygen saturation (SpO2) to lower than 3% below baseline. Reduced oxygen uptake is a key component of the pathology of OSA and contributes to daytime sleepiness and the long-term health consequences associated with OSA. ODI data was collected during overnight polysomnography on night seven of the treatment periods.
| ● | All three doses of IHL-42X reduced ODI compared to baseline to a greater extent than placebo. | |
| ● | For low and medium dose IHL-42X the difference in reduction in ODI relative to baseline compared to placebo was statistically significant (p<0.05) |
The greater reduction in ODI during IHL-42X treatment periods compared to placebo means that there is more oxygen in the subject’s blood during sleep while taking IHL-42X. This improves sleep quality and reduces risks of oxidative stress, bursts of the stress hormone cortisol, insulin resistance, altered metabolism and cardiovascular disease.
Table 4. Reduction in ODI compared to baseline during each treatment period.
| Reduction in ODI relative to baseline (least squares mean) | Reduction in ODI relative to baseline (%) | p value compared to placebo (Bonferroni adjusted) | ||||||||||
| Placebo | 1.8 | 18.3 | N/A | |||||||||
| Low | 11.7 | 59.7 | 0.021 | |||||||||
| Medium | 12 | 59.0 | 0.012 | |||||||||
| High | 8.32 | 28.5 | 0.162 | |||||||||
Incannex Healthcare Limited (ABN: 93 096 635 246)
Level 39, Rialto South Tower, 525 Collins Street, Melbourne VIC 3000
P: +61 409 840 786
Page 3 | 6
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Date: June 03, 2022 Public Announcement (NASDAQ: IXHL) (ASX: IHL) |
Plasma THC levels the morning after IHL-42X dosing
Countries that have set limits for THC above which driving is illegal have set those limits at 1-2 ng/mL (3-6). It is important to understand the clearance of THC after dosing with IHL-42X to determine where there will be an impact on ability to drive in countries where THC limits are in place. Plasma samples were collected 2 hours post dose 1 and the morning after dose 7 for each treatment period. Samples were analysed for concentration of THC using liquid chromatography with tandem mass spectrometry (LC-MS-MS).
The morning after dose 7, THC levels in the low dose IHL-42X samples had an average of 0.20 ng/mL and a maximum of 0.45 ng/mL. Both of which are below the thresholds for impaired driving. With medium and high dose IHL-42X the average THC concentrations the morning after dose 7 were 0.86 and 0.52 respectively.
Effect of IHL-42X on patient reported sleep quality
Each morning of the clinical trial, subjects recorded their sleep quality for the previous night as very poor, poor, fair, good, or very good. To compare patient reported sleep quality, the proportion of subjects who reported good or very good sleep each night was averaged across each treatment period. During the IHL-42X treatment periods subjects more frequently reported that their sleep quality was good or very good than placebo. The highest level of patient reported sleep quality was observed with low and high dose IHL-42X (Table 5).
Table 5. Patient reported sleep quality during each treatment period
| Proportion of subjects reporting good or very good sleep quality | ||||
| Placebo | 26.50 | % | ||
| Low | 49.49 | % | ||
| Medium | 38.47 | % | ||
| High | 50.13 | % | ||
Sleep metrics captured by actigraphy
For the duration of the clinical trial, subjects wore an Actiwatch, a watch-like device that uses actigraphy to capture data on activity and sleep. IHL-42X at all doses improved sleep efficiency (what percentage of time in bed a subject is asleep), the number of awakenings per night, and the total minutes the subject was awake during the night (WASO) compared to placebo (Table 6). These improvements were greatest for low and high dose IHL-42X. This means that while taking IHL-42X subjects were asleep for a greater proportion of time they were in bed and woke up less often.
Table 6. Sleep metrics captured by actigraphy
| Placebo | Low | Medium | High | |||||||||||||||
| Sleep efficiency | average | 76.83 | 84.81 | 81.34 | 84.17 | |||||||||||||
| p value compared to placebo | N/A | 0.0048 | 0.058 | 0.0078 | ||||||||||||||
| Awakenings per night | average | 49.31 | 35.8 | 41.44 | 37.33 | |||||||||||||
| p value compared to placebo | N/A | 0.0053 | 0.055 | 0.012 | ||||||||||||||
| WASO (min) | average | 62.59 | 37.55 | 47.22 | 38.55 | |||||||||||||
| p value compared to placebo | NA | 0.00011 | 0.0031 | 0.0010 | ||||||||||||||
Incannex Healthcare Limited (ABN: 93 096 635 246)
Level 39, Rialto South Tower, 525 Collins Street, Melbourne VIC 3000
P: +61 409 840 786
Page 4 | 6
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Date: June 03, 2022 Public Announcement (NASDAQ: IXHL) (ASX: IHL) |
Safety considerations
Adverse events were recorded from the time the subjects enrolled in the trial until their end of study visit. After recording of treatment emergent adverse events (TEAE) the study team, including investigators and medical monitors, reviewed the TEAEs to determine whether they were likely related to the investigational product. The TEAEs were consistent with what has been reported for dronabinol and acetazolamide alone. For each treatment period the proportion of subjects reporting one or more TEAEs (Table 7) as well as the total number of TEAEs (Table 8) were extracted from the clinical study report. Low dose IHL-42X had a similar proportion of subjects reporting TEAEs and a lower number of total TEAEs than placebo. This indicated that low dose IHL-42X is well tolerated.
Table 7. Proportion subjects of TEAEs reported for each treatment period
| Placebo | Low | Medium | High | |||||||||||||
| Total TEAE (%) | 81.8 | 33.3 | 55.6 | 66.7 | ||||||||||||
| Related TEAE (%) | 27.3 | 22.2 | 44.4 | 55.6 | ||||||||||||
Table 8. Total number of TEAEs reported during each treatment period
| Placebo | Low | Medium | High | |||||||||||||
| Total TEAE | 15 | 6 | 22 | 16 | ||||||||||||
| Related TEAE | 7 | 4 | 16 | 12 | ||||||||||||
References:
| 1. | Carley DW, Prasad B, Reid KJ, Malkani R, Attarian H, Abbott SM, Vern B, Xie H, Yuan C, Zee PC. 2018. Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea. Sleep 41. | |
| 2. | Schmickl CN, Landry SA, Orr JE, Chin K, Murase K, Verbraecken J, Javaheri S, Edwards BA, Owens RL, Malhotra A. 2020. Acetazolamide for OSA and central sleep apnea: a comprehensive systematic review and meta-analysis. Chest 158:2632–2645. | |
| 3. | https://www.justice.gc.ca/eng/cj-jp/sidl-rlcfa/qa2-qr2.html | |
| 4. | Vindenes, V., et al., (2012) Impairment based legislative limits for driving under the influence of non-alcohol drugs in Norway, Forensic Science International 219(1-3,)1-11 | |
| 5. | Wolff, K, et al., Driving Under the Influence of Drugs: Report from the Expert Panel on Drug Driving, Department of Transport, London, 2013. | |
| 6. | https://www.vifm.org/wp-content/uploads/VIFM-Annual-Report-2019-2020.pdf |
This announcement has been approved for release to ASX by the Incannex board of directors.
END
Incannex Healthcare Limited (ABN: 93 096 635 246)
Level 39, Rialto South Tower, 525 Collins Street, Melbourne VIC 3000
P: +61 409 840 786
Page 5 | 6
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Date: June 03, 2022 Public Announcement (NASDAQ: IXHL) (ASX: IHL) |
About Incannex Healthcare Limited
Incannex is a clinical stage pharmaceutical development company that is developing unique medicinal cannabis pharmaceutical products and psychedelic medicine therapies for the treatment of anxiety disorders, obstructive sleep apnoea (OSA), traumatic brain injury (TBI)/concussion, lung inflammation (ARDS, COPD, asthma, bronchitis), rheumatoid arthritis and inflammatory bowel disease. U.S. FDA approval and registration, subject to ongoing clinical success, is being pursued for each drug and therapy under development. Each indication represents major global markets and currently have no, or limited, existing registered pharmacotherapy (drug) treatments available to the public.
Incannex has a strong patent filing strategy in place as it develops its products and therapies in conjunction with its medical and scientific advisory board and partners. Incannex is listed on the Australian Stock Exchange (ASX) with stock code “IHL” and also has American Depository Shares listed on NASDAQ under code “IXHL”.
Website: www.incannex.com.au
Investors: investors@incannex.com.au
Forward-looking statements
This press release contains "forward-looking statements" within the meaning of the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements are made as of the date they were first issued and were based on current expectations and estimates, as well as the beliefs and assumptions of management. The forward-looking statements included in this press release represent Incannex's views as of the date of this press release. Incannex anticipates that subsequent events and developments may cause its views to change. Incannex undertakes no intention or obligation to update or revise any forward-looking statements, whether as of a result of new information, future events or otherwise. These forward-looking statements should not be relied upon as representing Incannex's views as of any date after the date of this press release.
Contact Information
Incannex Healthcare Limited
Mr Joel Latham
Managing Director and Chief Executive Officer
+61 409 840 786
joel@incannex.com.au
US IR Contact
Rx Communications Group
Michael Miller
+1-917-633-6086
mmiller@rxir.com
Incannex Healthcare Limited (ABN: 93 096 635 246)
Level 39, Rialto South Tower, 525 Collins Street, Melbourne VIC 3000
P: +61 409 840 786
Page 6 | 6
Exhibit 99.2
IHL - 42X ASX Ticker: IHL | NASDAQ Ticker: IXHL for treatment of obstructive sleep apnoea Phase II proof of concept clinical trial results. 03 June 2022
Disclosure and Disclaimer Not an offer of Securities This document has been independently prepared by Incannex Healthcare Limited (Incannex) and is provided for informational purposes only . This document does not constitute or contain an offer, invitation, solicitation or recommendation with respect to the purchase or sale of any security in Incannex . This document does not constitute an offer to sell, or a solicitation of an offer to buy, any securities in any jurisdiction (in particular, the United States), or a securities recommendation . This document is not a prospectus, product disclosure statement or other offering document under Australian law or any other law, and will not be lodged with the ASIC . Summary Information This document contains a summary of information about Incannex and its activities that is current as at the date of this document . The information in this document is general in nature and does not purport to be complete or to contain all the information which a prospective investor may require in evaluating a possible investment in Incannex or that would be required in a prospectus or a product disclosure statement prepared in accordance with the Corporations Act 2001 (Cth) (Corporations Act) . No Liability The information contained in this document has been prepared in good faith by Incannex, however no guarantee representation or warranty expressed or implied is or will be made by any person (including Incannex and its affiliates and their directors, officers, employees, associates, advisers and agents) as to the accuracy, reliability, correctness, completeness or adequacy of any statements, estimates, options, conclusions or other information contained in this document . To the maximum extent permitted by law, Incannex and its affiliates and their directors, officers employees, associates, advisers and agents each expressly disclaims any and all liability, including, without limitation, any liability arising out of fault or negligence, for any loss arising from the use of or reliance on information contained in this document including representations or warranties or in relation to the accuracy or completeness of the information, statements, opinions, forecasts, reports or other matters, express or implied, contained in, arising out of or derived from, or for omissions from, this document including, without limitation, any financial information, any estimates or projections and any other financial information derived therefrom . Statements in this document are made only as of the date of this document unless otherwise stated and the information in this document remains subject to change without notice . No responsibility or liability is assumed by Incannex or any of its affiliates for updating Not Financial Product Advice This document does not it constitute financial product advice or take into account your investment objectives, taxation situation, financial situation or needs . This document consists purely of factual information and does not involve or imply a recommendation of a statement of opinion in respect of whether to buy, sell or hold a financial product . An investment in Incannex is considered to be speculative in nature . Before making any investment decision in connection with any acquisition of securities, investors should consult their own legal, tax and/or financial advisers in relation to the information in, and action taken on the basis of, this document . Information in this Document is Confidential This document and the information contained within it are strictly confidential and are intended for the exclusive benefit of the persons to whom it is given . It may not be reproduced, disseminated, quoted or referred to, in whole or in part, without the express consent of Incannex . By receiving this document, you agree to keep the information confidential, not to disclose any of the information contained in this document to any other person and not to copy, use, publish, record or reproduce the information in this document without the prior written consent of Incannex, which may be withheld in its absolute discretion . Acceptance By attending an investor presentation or briefing, or accepting, accessing or reviewing this document you acknowledge and agree to the “Disclaimer” as set any information in this document or to inform any recipient of any new or more accurate information or any errors or mis - descriptions of which Incannex and any of its affiliates or advisers may become aware . Forward Looking Statements Certain information in this document refers to the intentions of Incannex, but these are not intended to be forecasts, forward looking statements or statements about the future matters for the purposes of the Corporations Act or any other applicable law . The occurrence of the events in the future are subject to risk, uncertainties and other actions that may cause Incannex’s actual results, performance or achievements to differ from those referred to in this document . Accordingly Incannex and its affiliates and their directors, officers, employees and agents do not give any assurance or guarantee that the occurrence of these events referred to in the document will actually occur as contemplated . Statements contained in this document, including but not limited to those regarding the possible or assumed future costs, performance, dividends, returns, revenue, exchange rates, potential growth of Incannex, industry growth or other projections and any estimated company earnings are or may be forward looking statements . Forward - looking statements can generally be identified by the use of words such as ‘project’, ‘foresee’, ‘plan’, ‘expect’, ‘aim’, ‘intend’, ‘anticipate’, ‘believe’, ‘estimate’, ‘may’, ‘should’, ‘will’ or similar expressions . These statements relate to future events and expectations and as such involve known and unknown risks and significant uncertainties, many of which are outside the control of Incannex . Actual results, performance, actions and developments of Incannex may differ materially from those expressed or implied by the forward - looking statements in this document . Such forward - looking statements speak only as of the date of this document . There can be no assurance that actual outcomes will not differ materially from these statements . To the maximum extent permitted by law, Incannex and any of its affiliates and their directors, officers, employees, agents, associates and advisers : • disclaim any obligations or undertaking to release any updates or revisions to the information to reflect any change in expectations or assumptions ; • do not make any representation or warranty, express or implied, as to the accuracy, reliability or completeness of the information in this document, or likelihood of fulfilment of any forward - looking statement or any event or results expressed or implied in any forward - looking statement ; and • disclaim all responsibility and liability for these forward - looking statements (including, without limitation, liability for negligence) . Results Presentation 2
Company statement Company statement on clinical trial results IHL42x has exceeded our expectations. It has shown substantial clinical benefit to people with obstructive sleep apnoea at the lowest dose given. This not only means people can get the full benefit with a reduced risk of side effects, but also, during the low dose treatment period every subject was substantially below the legal driving limits for THC in their blood the morning after dosing, thus removing a significant hurdle for IHL - 42X’s widespread use. Results Presentation 3
Unmet Medical Need Obstructive sleep apnoea (‘OSA’) OSA involves the narrowing of the upper airway during sleep, which interferes with a person’s breathing. Decreased oxygen uptake results in poor - quality sleep. Untreated OSA leads to serious long - term adverse health outcomes including hypertension, cardiovascular disease, heart attack, cognitive impairments, anxiety and depression, irritability and daytime fatigue increasing the risk of accidents. There are no pharmacotherapy (drug) treatments available to those afflicted. The current ‘standard of care’ is the Continuous Positive Airway Pressure (CPAP) machine, however, patient compliance to CPAP is low due to various factors related to patient discomfort. Results Presentation 4
Opportunity IHL - 42X Obstructive Sleep Apnea Problem OSA leads to serious long term adverse health outcomes but is also grossly undertreated . It is a highly prevalent condition and current treatment options (machines and devices) have poor patient compliance . Solution IHL - 42X has two pharmaceutical ingredients (THC and Acetazolamide) that target different aspects of OSA. Combined, these ingredients create a synergistic therapeutic effect, reducing the effects of OSA with low doses of each compound, minimising potential side effects and satisfying THC limits for impaired driving. No available pharmacotherapies Unblinded and confidential interim clinical data provided to the patent examiner. Patent claims considered novel and inventive. Clinical development status (1) https:// www.grandviewresearch.com/industry - analysis/sleep - apnea - devices - market Addressable market Annual Growth Rate U S $ 1 0 B ( 1 ) 6 . 2 % ( 1) people globally have sleep apnoea OVER 900M Asset Preclinical Australian Phase 2 POC FDA Pre - IND FDA IND FDA bioequivalence study FDA Phase 2 FDA Phase 3 Anticipated Milestones IHL - 42X Obstructive Sleep Apnea* Proposed open IND Q4 2022 Results Presentation 5
Milestones achieved Completed proof of concept phase 2 clinical trial – Results indicate that IHL - 42X is effective at reducing AHI in patients with OSA and is well tolerated. – IHL - 42X also reduced oxygen desaturation index, and improved patient reported sleep quality and the number of awakenings during the night. – The morning after dosing with low dose IHL - 42X, THC levels in blood were below the prohibited limit for driving. Feedback received from FDA at pre - IND meeting – Incannex do not require animal studies to open IND – Guidance was provided on the data that needs to be included in the IND application as well as design of pivotal clinical trials. IHL - 42X patent filed and international search report and opinion deemed key claims to be novel and inventive. IHL - 42X Development Progress Results Presentation 6
Opportunity Key Observations from phase 2 clinical trial – patients treated and concept confirmed 01. IHL - 42 X in low dose form outperformed medium and high dose with respect to sleep, THC clearance and safety . 02. Low dose IHL - 42X reduced average Apnoea Hypopnea Index (‘AHI’) by an average of 50.7% versus baseline; 25% of participants experienced greater than 80% reduction in AHI. 03. In low dose IHL - 42X samples, THC concentrations in blood were below the limits for impaired driving the morning after dose administration on night 7. 04. No serious treatment emergent adverse events were reported during the clinical trial. Apnoea hypopnea index (AHI) is the main measure for diagnosis and monitoring of disease, in patients with OSA. It is a serious sleep disorder in which breathing repeatedly stops and starts. Results Presentation 7
– Carbonic anhydrase inhibitor. – Used to treat glaucoma, altitude sickness, epilepsy and other indications. – Increases the difference between prevailing PCO2 and apnoeic PCO2. – Demonstrated as an effective treatment for OSA in 14 clinical studies. – AHI reduction was 23.9 - 27.6% relative to baseline with 250 mg dose. Strategic composition of dronabinol and acetazolamide makes IHL - 42X an exciting novel potential treatment for OSA. – Synthetic form of ( - ) - trans - Δ9 - tetrahydrocannabinol (THC). – Approved in US for treatment of HIV/ AIDS induced anorexia and chemotherapy induced nausea and vomiting. – Dampens afferent vagal feedback, stabilizes respiratory patterns and dilates upper airway – Two clinical trials to demonstrate effectiveness in reducing AHI in patients with OSA. – AHI reduction with 2.5 mg dronabinol was 23.4 %. Dronabinol Acetazolamide Low dose IHL - 42X (2.5 mg dronabinol and 125 mg acetazolamide) reduced AHI to a greater extent than reported for its constituent pharmaceutical ingredients. Low Dose IHL - 42X was observed to reduce AHI by an average of 50.7%, indicating synergistic effect and a novel patent opportunity. Results Presentation 8
Clinical Trial Incannex’s proof of concept clinical trial to assess the safety and efficacy of IHL - 42X in patients with OSA. Compared three doses of IHL - 42X to placebo at reducing AHI compared to baseline (primary endpoint). Other assessments included: – Oxygen desaturation index – Plasma THC levels – Patient reported sleep quality – Sleep metrics captured by actigraphy – Safety IHLOSAPOC1 Results Presentation 9
Baseline Placebo period IHL - 42X period 1 Results Presentation 10 IHL - 42X period 2 IHL - 42X period 3 Random order of low, medium and high dose IHL - 42X Study Design Observation – Four period cross over study. – Participants had OSA confirmed at baseline, once eligibility was confirmed they completed a single blind placebo treatment period followed by three double blind IHL - 42X treatment periods. – Each treatment period was seven days with an overnight sleep study on night seven to determine AHI and collect secondary endpoint data. – Treatment periods were separated by seven - day washout periods . – Adverse events were recorded and monitored for the duration of the study .
Demographic Results (Mean (Range)) Age 51.82 (39 - 64) Sex (female) 3/11 Childbearing Potential (Yes) 1/11 Race 10 White, 1 Asian Ethnicity Not Hispanic or Latino 100% Height (cm) 178.16 (160 - 187.3) Weight (kg) 92.23 (66.8 - 117) BMI 28.93 (24.9 - 36.9) Education (coded from 1 - 6)* 3.73 (1 - 6) Marital Status 5 Married, 1 Never Married, 3 Divorced, 2 Domestic Partner Handedness (Right) 10/11 English as Native Language (Yes) 10/11 AHI at baseline 42.8 Participant demographics *Education was coded with the following: 1 = 9th Grade; 2 = 12th Grade Diploma or GED; 3 = Some College, No Degree; 4 = Academic Associate Degree; 5 = Bachelor’s Degree; 6 = Master’s Degree Results Presentation 11
IHL - 42X reduced AHI at a group level. Results – Low dose IHL - 42X was the most effective dose strength with an average reduction in AHI of 50.7% compared to the baseline. – When comparing the means of the treatment groups, the difference observed for both low and medium dose compared to baseline was statistically significant (p<0.05). Results Presentation 12
IHL - 42X reduced AHI when compared within participants. Results – 25% of participants experienced greater than 80% reduction in AHI. – All three doses of IHL - 42X led to a statistically significant (p<0.001) reduction in AHI compared to placebo when calculated directly to each participant’s baseline. – Low dose IHL - 42X treatment led to a reduction relative to baseline in AHI of >50 % in 62.5% of participants and >80% in 25% of participants. Results Presentation 13
Baseline Placebo Low Medium Summary of AHI data During IHL - 42X treatment periods AHI was reduced compared to baseline and placebo treatment periods. – This means that when treated with IHL - 42X, the subjects’ breathing was interrupted less frequently during sleep. – This supports Incannex’s hypothesis that IHL - 42X is an effective treatment for OSA. Low dose IHL - 42 X was more effective at reducing AHI than either the medium or the high dose . – This is encouraging for Incannex’s development of IHL - 42X as a lower dose will reduce the risk of side effects and the cost of goods. Results Presentation 14
IHL - 42X reduced AHI to a greater extent than reported for acetazolomide and dronabinol as monotherapies. Results – IHL - 42X at a low and medium dose reduce AHI to a greater extent relative to baseline than acetazolamide (1) and dronabinol (2) at equivalent doses (based on extrapolation of published data with linear dose response curves with R2 values of 0.93 and 1 for acetazolomide and dronabinol respectively). 1. Schmickl CN,et. al. 2020. Acetazolamide for OSA and central sleep apnea: a comprehensive systematic review and meta - analysis. Chest 158:2632 – 2645. 2. Carley DW,et. al. 2018. Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea. Sleep 41 Results Presentation 15
Baseline Placebo Low Medium Summary of comparison with dronabinol and acetazolamide Low and medium dose IHL - 42X reduced AHI to a greater extent than reported for dronabinol and acetazolamide monotherapies at equivalent doses. – This supports Incannex’s hypothesis that dronabinol and acetazolamide are acting synergistically to treat OSA . – This data provides Incannex with confidence that IHL - 42 X will meet the FDA’s combination rule where both APIs must contribute to the therapeutic effect of a fixed dose combination product . – This supports Incannex’s hypothesis that IHL - 42 X is an effective treatment for OSA . Results Presentation 16
IHL - 42X reduces oxygen desaturation index (ODI). Results – IHL - 42X at a low and medium dose led to reduction in ODI of 59.7 and 59.0% respectively. These reductions were statistically significant (p<0.05). Results Presentation 17
Baseline Placebo Low Medium Summary of ODI data Low and medium dose IHL - 42X significantly reduced oxygen desaturation index during sleep. – This means that during low and medium dose IHL - 42X treatment, subjects had more oxygen in their blood – Low oxygen saturation, or high oxygen desaturation, can lead to: – oxidative stress which can damage cells and tissues – bursts of the stress hormone cortisol – insulin resistance and increased risk of diabetes – altered metabolism – Increased risk of cardiovascular disease Results Presentation 18
– THC levels in blood samples collected the morning after dose 7 were below the limit of detection (0.1 ng/mL) in 37.5 % of low dose IHL - 42X samples. 1. https:// www.justice.gc.ca/eng/cj - jp/sidl - rlcfa/qa2 - qr2.html 2. Vindenes, V., et al., (2012) Impairment based legislative limits for driving under the influence of non - alcohol drugs in Norway, Forensic Science International 219(1 - 3,)1 - 11 3. Wolff, K, et al., Driving Under the Influence of Drugs: Report from the Expert Panel on Drug Driving, Department of Transport, London, 2013. 4. https:// www.vifm.org/wp - content/uploads/VIFM - Annual - Report - 2019 - 2020.pdf Results THC clearance – The average THC concentration in blood samples from the morning after night 7 in the low dose IHL - 42X treatment period was 0.20 ng/mL. – The highest THC concentration detected in a sample from the low dose group was 0.45 ng/mL. Country THC blood concentration above which driving is prohibited Canada 1 2 ng/mL Norway 2 1.3 ng/mL UK 3 2 ng/mL Ireland 4 1 ng/mL Germany 4 1 ng/mL Results Presentation 19
Baseline Placebo Low Medium Summary of THC clearance Countries that have levels of THC in blood above which driving is prohibited have set limits at 1 - 2 ng/mL. The morning after low dose IHL - 42X 37.5% of subjects had no detectable THC in their blood. In the low dose blood samples that did have detectable THC the average concentration was 0.20 ng/mL and the maximum was 0.45 ng/mL, both of which are below the permissible limits. The THC clearance data indicates that low dose IHL - 42 X is unlikely to pose a risk for patients to legally drive while using the drug to treat their sleep apnoea . Results Presentation 20
IHL - 42X improved patient reported sleep quality. Results 1. Schmickl CN,et. al. 2020. Acetazolamide for OSA and central sleep apnea: a comprehensive systematic review and meta - analysis. Chest 158:2632 – 2645. 2. Carley DW,et. al. 2018. Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea. Sleep 41 – Participants recorded their sleep quality or satisfaction every night through out the study as very poor, poor, fair, good or very good. – During IHL - 42X treatment periods, the percentage of participants that ranked their sleep as good or very good was increased, compared to placebo. This is an average across the seven nights of each treatment period, for all the participants. Results Presentation 21
Results IHL - 42X improved sleep metrics captured by actigraphy (wearable sleep monitor). During IHL - 42X treatment periods, subjects were asleep for a greater proportion of their time in bed (sleep efficiency) (1) woke up fewer times (2) and were awake for less time (wake after sleep onset (WASO) (3) than during the placebo treatment period. (1) (2) (3) Results Presentation 22
Baseline Placebo Low Medium Summary of sleep quality During IHL - 42X treatment periods subjects reported a higher level of sleep satisfaction than placebo periods. Data from the Actiwatch indicated that subjects were sleeping through the night better than during the placebo period. These data support that IHL - 42X improved sleep quality, despite a lack of improvement in secondary endpoints that focused on sleepiness, mood and quality of life. Results Presentation 23
IHL - 42X was well tolerated. Results – No serious treatment emergent adverse events (TEAE) were reported during the study. – Low dose IHL - 42X had the lowest proportion of participants reporting TEAEs and the fewest number of total TEAEs compared to other treatment groups. – One participant on high dose IHL - 42X had a TEAE that caused them to be withdrawn from the study. However, they tested positive for illicit substances other than cannabis. – One participant on placebo had a severe TEAE that was not linked to the study drug . Results Presentation 24
Baseline Placebo Low Medium Safety summary IHL - 42X was well tolerated across all three dose levels. Results Presentation 25 – No serious adverse events (side effects) were reported during the study. – The only severe adverse event was reported during the placebo treatment period and was not linked to the study drug. Adverse event rates during the low dose IHL - 42X treatment period were lower than even placebo. These results support Incannex’s hypothesis that combining dronabinol and acetazolamide into IHL - 42X will reduce the potential for side effects.
Results Conclusions 01. Data from phase 2 proof of concept clinical trial supports the potential of IHL - 42X as an effective and well tolerated treatment for OSA, meeting the unmet needs of millions of people. 02. IHL - 42X reduced AHI, improved sleep quality with respect to both patient reported outcome and actigraphy, and did not lead to any adverse events beyond those expected based on what was expected from dronabinol and acetazolamide. 03. Low dose IHL - 42X was the most effective of the doses tested in this study. – It reduced AHI by over half (on average) in trial participants and 25% of participants saw an 80% reduction in AHI. – Low dose IHL - 42X has the lowest number of reported adverse events, even lower than placebo. – Low observed THC blood concentration amongst participants below limits for impairment to drive. 04. Patent application for IHL - 42X considered “novel and inventive” by international patent examiner. 05. Pre - IND meeting completed with FDA and the next major development milestone for IHL - 42 X will be the commencement of the IND opening clinical trial . Results Presentation 26
Acknowledgments Dr Jen Walsh and the team at UWA Centre for Sleep Science for work as a clinical trial site. Prof Terry O’Brien and the team at The Alfred for work as a clinical trial site. Novotech for managing the trial and study data. Agilex for analysis of samples for THC and metabolite levels. Results Presentation 27
Media Enquiries For media related enquiries please contact: Joel Latham joel@incannex.com.au Investor Enquiries For investor related enquiries please contact: Brad Dilkes investors@incannex.com.au Partnership Enquiries For partnership related enquiries please contact: admin@incannex.com.au incannex.com.au Results Presentation 28