Our Mission and Vision

Momoka Hayashi

Colorectal cancer: an unmet need

Colorectal cancer is one of the major causes of death worldwide, accounting for 15,708 deaths in the UK in 20101.
The vast majority of colorectal cancer cases are associated with lifestyle choices, with genetics only being the
cause for less than 5% of cases2. While the current risk of developing colorectal cancer is about 1 in 20, the
number of cases is expected to increase rapidly with the rise in obesity and ageing population. The demand for
efficient therapies has therefore never been more important.
Sulis Biotechnologies
Sulis Biotechnologies is a UK-based company specialising in drugs for cancer. Headquartered and founded in
2012 in Bath, Sulis Biotechnologies was established by William Cunningham, Momoka Hayashi, Natasha LambGuhren, Emma Lampard, and Corinne McEwan. The team has a collective background in chemistry, biology,
business management, accounting, and patent law.
Development of SUL002
At Sulis Biotechnologies, we have developed SUL002, a novel, orally administered antimetabolite to be used in
colorectal cancer chemotherapy. SUL002 is an optimised form of SUL001, a compound obtained from Medicines
for Malaria Ventures Malaria Box. Ordered free of charge by the University of Bath Biology Department in
2011, the Malaria Box contains a vast collection of potential antimalarial compounds intended to aid the research
of malaria. Due to the ability of some antimalarial and anticancer agents to inhibit the folate pathway, the potential
use of SUL001 and subsequently SUL002 was studied using colorectal cancer cells.
Importance of SUL002
New mode of action: SUL002 is the first drug available to inhibit SHMT and the first of its kind to inhibit all
three enzymes of the dTMP cycle. Its ability to target multiple enzymes also decreases risk of resistance.
Orally bioavailable: Intravenous chemotherapy is currently the principal route of administration used to treat
colorectal cancer. In comparison, SUL002 can be orally administered, making it a more convenient form of
treatment for many patients.
Monotherapy: Currently recommended medications are mainly combination therapies, involving fluorouracil
combined with leucovorin, oxaliplatin, or irinotecan. SUL002 is available as a monotherapy, increasing
convenience for patients.
Mode of action
SUL002 is a multitargeted antifolate that inhibits the three key
enzymes of the dTMP cycle (see diagram3): dihydrofolate
reductase (DHFR), thymidylate synthase (TS), and serine
hydroxymethyl-transferase (SHMT). Suppressed expression of
the enzymes will lead to the inhibition of DNA synthesis. This
is particularly harmful to tumour cells and results in apoptosis,
due to their affinity to divide more rapidly than other cells.
Progress and impact
We at Sulis Biotechnologies are proud to be able to offer a new treatment to help patients with colorectal cancer.
With initial studies showing the efficacy of SUL002 in colorectal cancer patients, further large-scale clinical trials
are warranted. As cases of colorectal cancer are rising at an alarming rate, we expect the demand for new
therapeutic drugs to increase and the sales of SUL002 to reach 1 billion by 2025.

1

Office for National Statistics (ONS). Mortality Statistics: Deaths registered in 2010, England and Wales. London: ONS; 2011.
Watson, AJ, Collins, PD (2011). Colon cancer: a civilization disorder. Digestive diseases (Basel, Switzerland), 29 (2): 222-8.

2
3

Michael W. King. Synthesis of the Thymine Nucleotides. http://themedicalbiochemistrypage.org/images/thymidinesynthesis.jpg (20.04.2013)

Scientific Research Programme

Natasha Lamb-Guhren

Structure and design strategy:

Using the initial lead structure, Lipinskis
rules and in silico analysis of the binding
interactions in the active site, an
optimised lead structure is shown. The
tPSA has been increased to potentially
give an orally bioavailable and soluble
anticancer prodrug. The log P value has
also increased, providing additional
lipophilicity and stability when crossing
the cell membrane4.

Synthetic strategy (may be scalable) to prepare compounds for screening (in house)5:

Data to be obtained will include:

IC50 (nM), GI50 (nM), ED50 (nM)
Toxicity studies, efflux ratio
Pharmacokinetic profile (ADME studies)

Techniques required for further

optimisation:
In silico analysis and SAR models
Synthetic and analytical chemistry
Synthesis and purification
NMR (300 MHz)
Mass spectrometry
HTS against therapeutic area6

HTS biological screening (in house)4:

Human cancer cell lines
Enzyme inhibition assays

Biological testing in vivo (outsource):

Cancer cell assays in mouse models
Efficacy and bioavailability data
Dose-response data
Half-life data

Future work:
Optimised lead compounds to be studied
further in vitro and in vivo
Multigrams to be synthesised for testing

Antimalarial Drugs, Chemistry Development and Future Challenges (Antimal project), 2011, BIOTEC, Thailand Science Park
Xie, Y. et al., Tetrahedron Letters, 2008, 49, 2320-2323
6
Zang, R et al., International Journal of Biotechnology for Wellness Industries, 2012, 1, 31-51

Company Structure

Corinne McEwan

Type of premises - Rented laboratory space at Bristol and Bath Science Park
- Convenient location and readily available space
- Access to shared NMR and Mass Spec
soon
Company start-up

Existing infrastructure
Hire of specialist lab equipment available

Board of Directors

Scientific Advisory Board

Structure
CEO
CSO

Office Manager

Technicians
Research Support

Scientists

Biologists
Employment strategy

Secretaries

Medicinal/
Synthetic Chemists
Lead Optimisation

IT Technician

Process Chemists
Development

Create a dedicated website

Advertise in appropriate publications i.e. Chemistry World, Nature Jobs, New Scientist
Networking at conferences

Timeline of Appointments

Acquire
Funding

Secure + stock
laboratory

Patent to be filed

Synthesis of compounds for testing

Recruit Medicinal/
Synthetic Chemists
and Technicians

Recruit Process
Chemists

SCIENTISTS
Screening/ in vitro assays

MANAGEMENT

Recruit Biologists

Recruit Head of R&D

(CSO) and Secretarial Staff

Office and IT
Support Managers

Engage services of
Contract Research
Organisation for
Clinical Trial Support

CEO and Board

of Directors

UpScale

Financial Plan

Emma Lampard

Amount requested: 20M

Equity stake given up: 15%
Additional funding may also be acquired from government or charity grants. The amount of finance requested is
greater than that shown in the table below, so additional funding is available if any extra scientists need to be
drafted in on short notice in order to achieve milestones on time. If early screenings of our drug look promising, we
aim to renegotiate finance plans with investors after two years. We are also in talks with Bristol and Bath Science
Park regarding no or reduced rent, in exchange for a share in the company, leaving more money to be spent on
research.
Rent
Equipment
Chemicals
Operating Costs
Insurance
Staff
Scientific Services
Professional Services
Product Testing
Clinical Trials
Other Costs
Total

Year 1
223826
90178
48965
36594
1259632
237695
265893
19542
335620
48630
2566575

Year 2
239494
130758
81772
40253
1372999
287983
297800
21496
1208232
238287
3919074

Year 3
256258
189599
125928
48304
1496569
346792
333536
23646
2283558
2658459
667204
8429854

Estimated progress
Timescale / months
0

10

15

20

25

30

35

Target ID
Target Validation
Primary Screening
Secondary Screening
Lead Optimisation
Preclinical Testing
Formulation
Phase I Clinical Trials

Milestones are shown in the graph above. Scientific and commercial progress will be monitored by achievement of
these milestones in timescales shown in the scheme below. Employees will be offered bonuses to encourage hard
work to achieve milestones on time, and investors will be kept up to date with progress.
Progress will be monitored closely so that any problems can be addressed as soon as they occur. Comprehensive
insurance will be taken out to protect the company building, software, and equipment. Additionally, it will cover
liability from products in clinical trials, liability from premises and operations, workers compensation, as well as
theft. Risk will be reduced by having appropriate security measures in place.

Future Progress

William Cunningham

Financial forecast: Phase II to market

Phase II
Average years to completion: 1.5-2
Cost: ~10 million
Type of subjects: Volunteers and
Patients
Facility: Institution
Patient monitor: Clinical researcher
Dose: Therapeutic
Number of clinical-trial subjects: 100
300
Role: Evaluate effectiveness and safety

Phase III
Average years to completion: 2.5 years
Cost: ~$20 million
Type of subjects: Patients only
Facility: Multicentre trials, randomized and placebo controlled, doubleblind testing can be within market
Patient monitor: Clinical researcher and personal physicians
Dose: Therapeutic
Number of clinical-trial subjects: 1,0005,000
Role: Confirm effectiveness, side effects, compare to current treatments
2 successful trials required before submit for EMA/FDA approval

EMA/FDA approval
Time to completion: 0.5-2 years
Approval costs (Prescription Drug User Fee Act II fee and the remainder for preparation of the NDA or
BLA): 0.51.2 million+ (200,000 for the PDUFA II fee)
Recruitment of trial patients
1. Hire CRO (contract research organization) maintaining clear and exact communication
2. Setup an Earned value contract (EVC) flat rate per deliverable agreed upon before contract signing hire
competent CRO contract writer to input strict change orders into contract to prevent excessive costs
3. CRO responsible for administration of clinical trials
4. Indian CRO market currently oversaturated easier to sign EVC
5. Recruit 1-2 people to monitor foreign CRO or recruit a local CRO monitor staff with proven track record
6. Depending on the amount of funding secured may recruit a specialist CRO that oversees international CROs
Run two trials at least, one internationally with large sample set e.g. India, another smaller trial in western nation
Addressing ADMET issues
1. Recruit specialist part time scientist panel 2 or 3 individuals
2. Analyse possible areas of issues relating to drug category look at previous trials and analyse relevance to drug
3. Produce a 3 category scale per issue relating to severity and plan responses with estimated costings, estimated
likelihood and possible solutions
4. Investigate avenues available for emergency finding and potential share of company willing to sell per severity
level of ADMET issue
5. Issue document to stake holders
6. Construct decision trees per potential issue and per multiple parallel issues each with predicted outcomes and
probabilities
Management of clinical data
1. Recruit clinical data manager preferable one with a history with chosen CRO
2. Produce relevant standard operating procedures required for data storage, analysis and reporting
3. Depending on funding recruit statistical modeling team recruit from people unaffiliated to CRO or data
manager to maintain transparency and quality willing to question suspect data or practices
4. Draft a data management plan before initiation of clinical trials lease with chosen CRO to decide on most
efficient and reliable IT data management system in an attempt to align IT systems for efficiency
5. Recruit a dedicated QC role per department within company better than centralised QC department as more
efficient and enforces alignment from employees also builds rapport

Future Progress

William Cunningham

Formulation strategy
1. Initiate formulation development at start of phase 1 if enough capital or phase 2 to ensure completion of largescale formulation near the end of phase 3 trial
2. Acquire quotes from multiple contract formulation services for the development of our compound
3. Formulation must be stable for market to ensure patients receive the quoted dosage
4. Quality of formulation during phase 3 is paramount as results from trials will be greatly influenced by
consistency of tablets used to generate the data
Sales and marketing
1. Develop financial plan based approximately around the breakdown of marketing avenues: 50% costs towards
production of free samples, 25% information booklets aimed towards physicians, 12% on direct to user advertising,
7% on hospital detailing, and 6% on journal ads
2. Recruit pharmaceutical marketing specialist preferably with understanding of the legality of methods in different
regions
3. Recruitment of a top quality branding agency is fundamental to develop a sellable product. Should start as soon
as phase 1 finishes if there is a positive outcome
4. Depending on outcome of company sale to big pharmaceutical - if no interest is shown and the medicinal area is
viewed unfavorably at the time of phases 2 and 3 then in house soles representatives should start to be recruited and
clinicians contacted preparation for selling drug without collaboration with big pharmaceuticals
Further equity sources
1. Essential ***Recruit expert advisor in grant funding to provide extra money towards phase 2 and phase 3
financial requirements
2. Government venture capital is useful due to scarcity of private VC
3. Big pharmaceutical venture capital creates ties early that could be used later on as an exit strategy- also
provides valuable expertise in drug development and infrastructure more likely than private VC with current
economic situation
Exit strategy
1. Ideal plan is the RIPCO model (royalty-income pharmaceutical company) develop the drug to stage where in
place are the NDA, and solid IP then attempt to license the drug to big pharmaceutical in exchange for royalty on
sale.
Advantages to this are: substantial help given during final stages of commercialisation, facilities are in place for
launch and large cash reserves if unforeseen complications arise. Royalties gained can be further invested into next
project. Added bonus of recent patent cliff big pharmaceuticals looking for investments without requiring in depth
screening and lead optimisation can leverage big business advantages to help poorly positioned small biotech
2. The FIPCO model is a last resort if no interest is shown by a big pharmaceutical. It offers the greatest reward at
very high risk unlikely to succeed without second drug in pipeline and massive capital investment is required,
which is unlikely during this period of recession
3. Unlikely to achieve an IPO has advantages such as allows continuation of employment involves selling
private share to public making a publically listed company. High costs with process and transparency with sensitive
information required bad if research area is hotly contested