Forendo Pharma Innovating for endometriosis and for

Forendo Pharma
Innovating for endometriosis and
for “low T” in men
October 21st, 2014
Risto Lammintausta, CEO
Forendo Pharma in brief
Strong team
• Team has brought ospemifene from discovery to FDA approval in
Hormos. Today 9 FTE + 2 part time
• RL has led 6 drugs from discovery to launch in Farmos, Orion and
Hormos.
• Scientific basis from University of Turku, Professor Matti Poutanen as
co-founder
High value portfolio
• HSD17B1 inhibitor FP-5677: first targeted treatment for endometriosis
progressing to clinic. Opportunity for long-term, disease modifying
therapy.
• Fispemifene to normalize low testosterone, clinical POC shown,
partnered for USA with Apricus Biosciences.
17beta hydroxysteroid dehydrogenase type 1
(HSD17B1) inhibitor FP-5677,
First selective approach for treating endometriosis
and maintaining normal hormone balance
Endometriosis
Presence of endometrium-like tissue inside abdomen
• Begins after puberty with dysmenorrhea
and pelvic pain: delay to diagnosis 8 years
(USA), 65% misdiagnosed, treated with
analgesics
• Prevalence about 10% at fertile age
• 30-40% suffer infertility
• Annual cost in USA 70 billion US
Simoens et al., Hum. Reprod., 2012, 27:1292-1299
Endometriosis is an estrogen dependent disease
• From puberty up to menopause
• Most symptoms respond to complete estrogen ablation
– All current drugs act by decreasing systemic estrogens
• Recent emphasis on local synthesis of estradiol in the lesions
– Overexpression of estrogen synthesis enzymes found
– Slow elimination of estradiol in lesions
– HSD17B enzymes have key role in the local estrogen
overactivity
• Insufficient treatment or misdiagnosis allow progression to
adhesions and deep tumor-like lesions requiring surgery
But: no disease-modifying drug available for long-term use
The key competing products in development
• Oral GnRH antagonist in phase III
– Elagolix by Abbvie expected to become the leading brand
over the current injections
– Licensed from Neurocrine on 2010 after phase IIb for $75M
signing fee, 500M milestones and double digit royalty
– Challenge to balance safety/efficacy
• Steroid sulphatase inhibitor in phase IIa in combination with
progestin by Preglem/Gedeon Richter
– No efficacy data published
– Unspecific hormonal profile
• New progestin products
– Minor advantages over the existing ones
Forendo concept:
HSD17B1 enzyme leverages tissue estradiol level
OH
O
HSD17B1
HO
HSD17B2
Estrone (E1)
•low activity
• Expressed in
–
–
–
–
–
Endometrium, endometriosis Breast , most breast cancers
Uterine fibroids
Present in ovary with other HSD17Bs
In males only in prostate
• HSD17B2 eliminates estradiol
HO
Estradiol (E2)
•Highly active
Because of
HSD17Bs
Proliferative
endometrium has
E2 level 10x
over the serum,
luteal phase 1x
Forendo´s novel HSD17B1 inhibitor
• Targeted effect on endometriosis lesions
– In primate disease model HSD17B1 inhibitor
• eliminates endometriosis lesions
• reduces pain behavior
• maintains normal ovarian cycle
– Estradiol formation in human lesions ex vivo is blocked
by HSD17B1 inhibitor
• Unencumbered compositon of matter IP filed 2013
The expected clinical profile for FP-5677,
HSD17B1 inhibitor in endometriosis patients
• Serum E2 , progesterone , FSH and LH remain intact
• Uterine endometrium becomes atrophic leading to
amenorrhea and contraception
• Good efficacy of subjective symptoms with good tolerability
• Fertility recovered quickly after discontinuation
• Opportunity for long-term treatment to prevent progression of
the disease and need for surgeries
• First product to eliminate the local estrogen excess and
maintain normal ovarian function
Fispemifene
Novel SERM For Secondary Hypogonadism
To be progressed with partners
Serum “T” Increases to Normal Eugonadal Range
700
*
600
ng/dL
500
*
*
400
300
Placebo
(n=31)
Fispemifene
(n=37)
200
100
0
Baseline
Week 4
Week 8 Follow-up
* P <=0.001
Fispemifene Avoids Most Issues Associated with
Testosterone Replacement
• Once daily oral dosing
• Restores testicular function maintaining spermatogenesis
and reproductive status
• No risk of supra physiological T levels
• No risk of secondary exposure of children/women
• No decrease in size of testes
Boys with increasing estrogen/androgen ratios have
multiple symptoms to be treated with fispemifene
Expectations from Fispemifene
1. Partnering with Apricus Biosciences for USA
•
•
•
•
Development costs covered by Apricus, launch targeted 2018
documents available for RoW
Signing fee USD 12,5 M (5M cash, 7,5M shares)
Development milestones during 2016-18 about USD 40 M
Appropriate royalty and sales milestones
2. Partnering for the RoW expected during 2015/16
•
•
Minor extra studies needed for EMA by the partner,
10 year exclusivity
Significant interest from Japan and BRIC countries
Forendo Milestones Plan 2015-2017
• Novel HSD17B1 inhibitor to phase II POC in endometriosis
– First-in-class CTA by Q1/2015
– Proof of pharmacology in healthy women by Q2/2016
– Proof of clinical efficacy and safety in patients by
Q4/2017
• Fispemifene to phase III and partnerships for the main
markets
• Other products from the HSD17B inhibitors platform to be
brought to clinical development for different indications.
Summary
• Team with track record of bringing products from discovery
to the market from academic collaboration
• Novel product opportunity to transform the endometriosis
therapy
– First targeted and disease modifying mechanism
– To reduce need for surgeries
– TPP compatible with long term use
– Fully owned IP from 2013
– Clinical POC targeted after 3 years
• Another Phase II/III product to strengthen the cash flow
Contact
info:
Forendo Pharma
Ltd
Itäinen Pitkäkatu 4 B, FI-20520 Turku, Finland
[email protected]
+358 40 310 8000
www.forendo.com
[email protected]
www.forendo.com