Clinical stage pharmaceutical and medication systems company

Proprietary inhalation device for rapid and controlled drug delivery:
allowing easy-to-use rescue therapy with very fast onset-of action

Focus on therapeutic areas with “acute” unmet need

  One program marketed (Colistin Cyclops™ - cystic fibrosis)

• Compassionate use regimen
• Reimbursed by payers

Funds raised to date: €3.3M (equity)

Current investment round: €27.9 M*

  Use of proceeds by mid 2023

• Bring 2 lead clinical programs to submission/approval in the US and EU
• Advance 7 additional programs to Phase II/III clinical development

• Broad pipeline across key therapeutic areas with significant unmet need covering commercial and exploratory programs

      • Colistin Cyclops™ application (for cystic fibrosis-related infectious disease) marketed in the Netherlands under compassionate use regimen,

         reimbursed by payers

      • Lead programs Levodopa Cyclops™ (for neurology) and Epinephrine Cyclops™ (for allergy) pursuing accelerated regulatory routes to market in US and EU

      • Clinical-stage follow-on programs exploring applicability in respiratory indications with high unmet need such as COVID-19

Therapeutics programs based on Cyclops™ technology addressing unmet medical need

Therapeutic programs for Series A Investment Round are selected on the basis of:

• Potential to solving an ‘acute’ medical need (i.e. ‘rescue medication’)
• Market attractiveness
• Possibility to obtain marketing authorization via accelerated regulatory pathway, e.g. US 505(b)(2) route
• Opportunity for early exit: Series A funding covers lead programs until marketing authorization in initial marketing regions within 2-2.5 years

Company information

• HQ: Roden/Groningen (the Netherlands)
• Clinical stage pharmaceutical and medication systems
  company developing inhaled dry powder products
• Spin-off 2014 from University of Groningen and from
  medical device manufacturer IMDS
• Funds raised: €3.3M equity

• Cyclops™ technology

      • Proprietary dry powder inhaler

      • Design and functionality patent protected until 2034

      • CE marked medical device

• IP in-licensed from University of Groningen

Cyclops™ technology – IP and regulatory

Bram van Dijck, MBA – CEO

• Bram van Dijck held senior Commercial, Portfolio and General Management
• Positions at Grünenthal Group, Hospira, Teva Pharmaceuticals, Organon
  and Abbott Laboratories.
• He is also Adviser to several Pharma and MedTech companies.

Jeroen Tonnaer, PhD, CLP – CBDO

• Jeroen Tonnaer was previously CBO of Cristal Therapeutics, Executive Director at Merck/MSD, and held various prior BD&L and R&D positions at
  Schering-Plough and Organon.
• He is also member of the Advisory Board of Protinhi Therapeutics.

Reinier Schwietert, PhD – CSO

• Reinier Schwietert received his PhD degree (cum laude) in Pharmacology
  from the University of Amsterdam and thereafter fulfilled different
  (management) roles and responsibilities within the pharmaceutical industry. Since 2017 he also acts as an independent drug development consultant for small biotech companies.

Harry Heijerman, PhD, Professor – University Medical Center Utrecht (UMCU)

Head of Department of Pulmonary Diseases

Anne de Boer, PhD – University of Groningen (retired)

Project Leader Inhalation Group Department of Pharmaceutical Technology and Biopharmacy

Gerard Koppelman, PhD, Professor – Beatrix Children’s Hospital (UMCG)

Head of Pediatric Pulmonology and Pediatric Allergology

Daan Touw, PhD, Professor – University Medical Center Groningen (UMCG)

Head of Clinical Pharmacological Laboratory

Teus van Laar, PhD, Professor – University Medical Center Groningen (UMCG)

Medical Director of the Parkinson Expertise Center in Groningen

Geert Jan Groeneveld, PhD, Professor – Centre for Human Drug Research University of Leiden

Professor of Clinical Neuropharmacology

Bert Tuk, PhD – Tuk Management

Clinical Pharmacologist

Use

Cyclops™ Device

Drug Delivery
through Inhalation

• Non-invasive
• Easy to use
• Deep lung deposition
• Local application or rapid drug absorption into circulation

• User friendly, pre-loaded, disposable, credit card-size inhalation device
• Overcomes current inhaler limitations
  ✔ poor drug deposition
  ✔ dose limitation
• Poor motor skills don't affect use
• Cost-effective manufacturing
• CE marked – patent protected

 1. Remove cover foil

 2. Exhale

 3. Inhale

 4. Check delivery

Candidate

Preclinical

Phase I

Phase II

Phase III

Submitted

Marketed

Inbrija™

Follow-on programs

Lead programs qualify for regulatory routes allowing advanced marketing authorization

Other programs explore respiratory indications of significant unmet need

Levodopa is the cornerstone in the treatment of PD disease for well over 50 years.

It is the most effective, safe and well tolerated drug available to this end. 

Approximately

90%

Approximately

of young onset patients (less than 40 years old) develop off episodes after 5 years of taking levodopa.

However, patients suffering from PD will encounter a major unmet medical need as the disease progresses: 

Available medication has a slow or unpredictable onset of action or is poorly tolerated and uncomfortable to use.

Studies showed that PD patients are able to readily use Levodopa Cyclops™ during an OFF episode.

Levodopa Cyclops™ results in peak plasma concentrations within minutes and its absorption is less variable than that of oral levodopa, both of which are prerequisites for the rapid and predictable relief of OFF episodes.

Levodopa Cyclops™ offers PD patients easier and more convenient handling, and a faster and more predictable onset of action to counteract OFF episodes.

Patients in mid- and late-stage of disease suffer from variable therapeutic
efficacy resulting OFF-episodes

Currently available medication insufficient to effectively offer rescue
with fast onset of action

Rapid onset of action

Good control over levodopa plasma levels

Optimal flexibility regarding individual dose titration, ensuring better
efficacy and avoidance of dyskinesias

Phase II studies show fast and reproducible absorption of levodopa

Levodopa Cyclops™ can offer fast and reliable rescue treatment for Parkinson’s patients suffering from OFF-episodes

Phase II studies show faster absorption of levodopa compared to Inbrija®

The higher levodopa elimination rate following the use of Levodopa Cyclops™ is caused by the absence of a decarboxylase inhibitor during the studies

• FDA confirmed applicability of 505(b)(2) regulatory pathway
• Quick route to market – marketing authorization expected ≥2023
• Few (pre)clinical activities to be conducted for marketing authorization*:

     • Limited preclinical safety package L-Leucine excipient

     • Human factor study

     • Relative bioavailability study vs. reference listed drug Inbrija®

• Reference to dossier of reference listed drug Inbrija® possible as of December 2021

• Anticipated peak sales ~€300M (US only) -
  €700M (US+EU)

• Levodopa Cyclops™ substantially easier in use than Inbrija®

     • Better compliance

     • Better efficacy

• Business case indicates Levodopa Cyclops™ outperforms Inbrija® on price

     • Larger market share

      • Higher reimbursement rates

Anaphylaxis is on the rise, with the lifetime prevalence rates estimated at 0.3% in Europe  and at least 1.6% in

the US

Anyone who has ever had a severe allergic reaction or anaphylaxis is at risk of this happening again and is prescribed an epinephrine autoinjector for first-line rescue treatment

Anaphylaxis is a severe systemic allergic reaction, which if not treated promptly, may result in respiratory or cardiovascular shock and ultimately even death.

Less than 50% of persons at risk of anaphylaxis know how to use their autoinjector correctly.
What’s more, many people are reluctant to use their autoinjector, putting them at risk of untimely treatment. When they do use their autoinjector, there is a real risk of accidental exposure or device

failure.

Epinephrine Cyclops offers the solution: an easy-to-use, non-invasive device with an immediate onset of effect

• Immediate onset of action
• Short exposure allowing for repeated treatment without dose stacking
• Effective local treatment of symptoms of the airways and oropharyngeal region
• Easy to use

Allergic subjects are reluctant to use available invasive autoinjector devices (EpiPen) putting them at risk of untimely treatment of an anaphylactic reaction

Less than 50% of subjects at risk of anaphylaxis can use their autoinjector
device correctly

Non-invasive & easy to use

Immediate onset of action

Effective local treatment of symptoms of the airways and
oropharyngeal region

Short exposure allowing for repeated treatment without dose stacking

Active substance

Mode of administration

Tmax

Clinical onset of action*

Efficacy

Side effect profile

*
**
***
****

as defined by a significant (p<0.05) improvement in UPDRS III motors score compared to placebo post-dose
LeWitt et al. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson’s disease:
a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet Neurology (2019) 19: 145 - 154
Olanow et al. Apomorphine sublingual film for off episodes in Parkinson’s disease: a randomized, double-blind, placebo-controlled phase 3 study. The Lancet Neurology (2020) 19: 135 - 144
Pfeiffer et al. The APO302 Study Investigators. Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson's disease. Parkinsonism & related disorders (2007) 13: 93-100

Levodopa Cyclops™

Levodopa

Inhalation

10 min

< 10 min
(based on PK)

Better than Inbrija™ (based on PK)

Mild cough

+++++

Inbrija™

Levodopa

Inhalation

30 min

30 min**

Moderate

Cough

+

Kynmobi™

Apomorphine

Sublingual

51 min

15 min***

Good

Nausea and oral lesions (30% of PD patients do not tolerate treatment)

++

Apokyn™

Apomorphine

SQ Injection

23 min

10 min****

Good

Nausea and injection site reactions

-

Ease of self-administration

Phase I study shows immediate and reproducible absorption of epinephrine

Epinephrine Cyclops™ can offer fast and reliable rescue treatment for
subjects at risk of anaphylaxis

• Decentralized procedure with Sweden as reference member state
• Swedish Authority to confirm applicability of hybrid regulatory pathway
• Quick route to market – marketing authorization expected ≤2023
• Few clinical activities to be conducted for marketing authorization*:
  • Phase II efficacy study in 40 subjects
  • Human factor study
• Reference to dossier of reference listed drug EpiPen®

• Current sales competitor EpiPen ~$200M
• Total addressable market €2.3B

• Epinephrine Cyclops™ offers a needle-free substitute for EpiPen® and other autoinjectors
• Epinephrine Cyclops™ is substantially easier in use than EpiPen®

Prioritized strategic development programs

• Levodopa Cyclops™: €11.6M – US market
• Epinephrine Cyclops™: €2.3M – EU market
• Capital need prioritized programs: €13.9M

Optional expansion programs

• Levodopa Cyclops™: €9.7M – expansion to EU market
• Epinephrine Cyclops™: €4.3M – expansion to US market
• Capital need optional expansion programs: €14.0M

→ Capital need for both programs: €27.9M*

• Levodopa Cyclops™: anticipated peak sales ~€300M (US only) - €700M (US+EU)
• Epinephrine Cyclops™: current sales competitor EpiPen ~$200M;  total addressable market €2.3B

Candidate

Preclinical

Phase I

Phase II

Phase III

Submitted

Marketed

Inbrija™

Follow-on programs

2 programs approved / under approval

7 additional programs in Phase II/III