People | Product | Potential Special Edition on the World’s Indigenous People International Day

We caught up with John Boghossian, CEO, Director, and co-founder at Kanna Health, a preclinical stage biotech start-up developing novel therapeutics inspired by the active alkaloids from the native South African plant species, Sceletium tortuosum, also known as Kanna. Kanna Health’s lead compound is about to enter first-in-human studies for premature ejaculation.

The purpose of the article series ‘Product | People | Potential’ is to feature and showcase the very best UK start-ups with great potential, truly inspiring businesses that are shaking up their sector. We capture and share the stories behind the name. We collate authentic peer to peer real-talk, while celebrating the growth and success thus far and gather a glimpse of what’s ahead.

Jazz@ADLIB: Hi John, nice to meet you. Can you please introduce yourself, what your business does, what stage you are at currently and what makes your business and offering unique?

John: Hi Jazz, it is nice to meet you too. I am the CEO, Director and co-founder at Kanna Health where I have been for the last 18 months. Prior to this, I worked at another nature-inspired biotech company, COMPASS Pathways, focused on the development of psilocybin – the active ingredient in “magic mushrooms” – for psychiatric and mood disorders. I have a passion for life sciences entrepreneurship, in particular developing novel therapeutics based on natural products such as psychedelics and other botanical plants with traditional medicinal uses.

Kanna Health is a preclinical stage biopharma company developing novel therapeutics across a range of indications from psychiatry to sexual health, based on the pharmacological properties of alkaloids and novel compounds derived from Sceletium tortuosum, commonly known as kanna. Kanna is a South African medicinal plant with centuries of traditional use for mood and performance enhancement by the San and Khoikhoi communities in South Africa.

Our lead programme is focused on developing a unique proprietary form of a naturally-occurring alkaloid from kanna, KH-001, as an on-demand treatment for premature ejaculation. There are currently limited treatment options (and no FDA approved oral options) available for the 20-30% of men impacted by this distressing condition globally.

Jazz@ADLIB: Can you share the story behind the origin of your business and product, how did it all begin?

John: The first written report documenting kanna use was from the Dutch Commander of the Cape settlement in 1662. Since then, the plant has been explored further by other scientists and researchers, including our CSO and co-founder Dr Nigel Gericke. Nigel is a world expert in the ethnopharmacology of kanna, with more than 50 publications in the field over the past 30 years.

As mentioned, kanna has been used historically for a wide variety of applications. These traditional uses fascinated me and my co-founders, Dr Ryan Protzko and Lars Wilde, and formed the basis for the subsequent founding of the company. The identification of our lead indication, premature ejaculation, was somewhat serendipitous. Our experimentation with kanna was initially to investigate its neurological effects, however, an impact on time to ejaculation was discovered as a side-effect! Our story holds parallels to the discovery of Viagra for erectile dysfunction. We later validated this effect in a proof-of-concept study in rats. Given there is currently no FDA-approved oral medication for this prevalent condition, and some downsides to current offerings elsewhere, we saw an opportunity to address an important unmet need. We brought Nigel on board, as well as other leading scientists and experienced entrepreneurs, to turn this idea into a reality.

We have raised close to $10 million to date to bring our lead compound into the clinic, invest in our discovery programme and further build our team. As a company, we are also socially conscious and want to ensure that kanna’s traditional knowledge holders in South Africa also benefit from our mission from the start.

Jazz@ADLIB: Speaking of people, can you share how you involve traditional knowledge holders and ensure that they benefit from your venture? Do you have any learnings to share with other businesses developing products of natural origin and historical use by indigenous peoples?

John: Thanks to Nigel’s network, we have been able to involve traditional knowledge holders in our work from the outset. Nigel has been key to forming and growing our partnership with the South African San Council (SASC), a body established in 2001 to ensure the fair representation of the San people on both a national and global stage.

One of the company’s core values is to acknowledge and celebrate the cultures that have inspired and enabled our development. August 9th marks the International Day of the World’s Indigenous People, and the announcement of Kanna Health’s first impact initiative, with the signature of a benefit-sharing agreement with the SASC. This agreement provides regular payments to the SASC and focuses on recognising the San people as the primary traditional knowledge holders in relation to the medicinal uses of kanna. The rural community of Paulshoek/Nourivier in South Africa has been specifically acknowledged by Kanna Health and the SASC as a secondary beneficiary of rights, for the detailed ethnobotanical information they provided to Kanna Health. We have submitted the benefit-sharing agreement to the South African Development of Environmental Affairs for approval.

Recently, we were delighted to have Nigel attend in person at the signing ceremony held at the San heritage centre, !Khwa ttu, which preserves the San culture and education. Following his visit with the SASC, Nigel reported:

This best-practice agreement stands as an example of how a benefit-sharing agreement can be concluded with local communities by the biotech industry that utilises indigenous plant use knowledge as a departure point for pharmaceutical drug discovery and development. Transferable key elements of the negotiations leading to this benefit-sharing agreement include the existence of historical records of plant use, a recognised body representing the beneficiary community, mutual good faith, transparency and trust, frank and open dialogue, and experienced independent legal counsel engaged by the beneficiaries.”

The Secretary General to the SASC, Collin Louw, also said:

The San Council of South Africa believes in long-term partnerships and collaborations, and our continued friendship with Dr Nigel Gericke is testimony to that. Ethical and transparent benefit-sharing negotiation based on our principles of respect, honesty, fairness, and care is paramount to any benefit-sharing agreement. The partnership with Kanna Health is a benchmark for benefit-sharing agreements with international companies. They have been transparent with the project and company information, updating us on the project development, sharing research data and remaining frank about potential project developments.”

With regards to learnings to share with other businesses; whilst developing Kanna Health, we learned the importance of including and learning from traditional knowledge holders from the get-go, as well as abiding by the Nagoya Protocol* and other international bioprospecting standards.

Working with knowledge holders teaches us about the human subject experience, which can help accelerate new discoveries and support study design decisions. Abiding by the Nagoya Protocol allows us to give back to the communities that have cultivated this knowledge for centuries through “benefit sharing”, such as royalties.

We intend to build a long-term relationship with the San people based on mutual trust, so that both sides can benefit from the collaboration.

*Jazz@ADLIB: What is the Nagoya protocol?

John: It is an international agreement that aims to share the benefits from using genetic resources, traditional knowledge associated with genetic resources, and the benefits from using these resources.

Jazz@ADLIB: Moving to product, how has the historical and traditional use of kanna impacted your approach to product development?

John: Historical use provides a rich and interesting source of anecdotal evidence, which can provide an indication as to potential mechanisms of action, target indications, and potential adverse effects. For example, kanna has been traditionally used for a variety of purposes; from mood-related disorders, to combating stress, and from relieving thirst and hunger, to tackling fatigue. This has led our team to search for treatments for related modern-day illnesses using specific compounds from the plant.

The evidence we have from reports, case studies, and Dr Gericke himself, has allowed us to significantly accelerate our drug development process to date. It enables us to identify potential lead compounds and indications and proceed rapidly to proof-of-concept, whilst anticipating a relatively benign safety profile. Whilst historical and anecdotal reports are not sufficient to negate the need to conduct a full battery of safety studies, we have been able to execute this in a more streamlined and focused manner, in consultation with the UK pharmaceutical regulator the MHRA. By harnessing traditional knowledge of the medicinal properties of the plant, we have been able to accelerate our development timeline and we hope to provide new treatments to patients quicker.

Looking beyond the programme for our lead compound, KH-001, the kanna plant contains multiple other active alkaloids that are of interest and have provided inspiration for novel compounds within our product discovery programme.

Jazz@ADLIB: And then potential, can you share your views on some of the opportunities and challenges of developing therapeutic applications from natural origins?

John: As discussed in the question above, one of the biggest benefits of developing natural compounds is access to anecdotal evidence. This provides a starting point for development, accelerating the overall timeline, and hopefully enables a higher early-stage probability of success, thus allowing for quicker access to new treatments for patients. We will have to wait and see if Kanna Health can prove this claim to be true as we progress our programmes over the next few years!

The trend towards public preference for products of natural origin is another benefit of this field, as well as the ability to work with and give back to communities that have cultivated medicinal plants for centuries. If we are successful, we can really help to raise the profile of these indigenous cultures and protect their future.

Developing medicines from natural origins also presents a number of unique challenges. The supply chain for this rare botanical is fraught with risk born from the seasonality of the crops, huge variation in composition and yield of material from different harvests, and the potential for crop failure due to bad weather, disease or pests. We mitigate this risk through the development of a proprietary synthetic route, however, the chemistry is highly complex and the task far from simple.

Intellectual property (IP) is the other area of challenge. Usually, the natural product is a known entity, often with a history of use to help treat certain medical conditions, with potential preclinical or clinical studies already published. This raises the bar for protecting the compound and its utility, given barriers may restrict new entrants’ freedom to operate in certain areas. This alone often deters biopharma companies from trying to develop nature-inspired medicines.

We are fortunate at Kanna Health to have a legal team with significant experience in developing robust and durable IP for natural products. This involves conducting an extensive review of the areas that present potential opportunities for IP protection, be it in the compound itself, how it is used or made, or other patentable characteristics such as product-specific exclusivity. We plan our development programmes to ensure that we are optimising the touchpoints to create robust IP for all of our natural products. The key, we have found, is to have an IP-forward approach to product development and include IP decisions as gateways to further early product development.

Jazz@ADLIB: What are the next steps?

John: We are gearing up for our first-in-human study (Phase i) for KH-001 in premature ejaculation to be conducted in the UK starting early next year.

Whilst our first impact initiative is signing the benefit-sharing agreement with the SASC, this is most definitely not our last! We will be focused on developing a portfolio of social and environmental initiatives, and growing an even closer relationship with the San people.