DEP Docetaxel: Well here it is, the sixth in a series of posts that examine what we know about internal DEP development candidates. I have put this material together in hopes that it will be of use to the community. I hope you will take some time to see the, yes long, but also exciting emergence of the first DEP product, DEP docetaxel. This could potentially be a real life saver for many individuals.
Material has been highlighted for ease of finding information. There is a lot of history here so some emissions could exist. Language has been directly lifted from Starpharma publications.
Hyperlinks have also been added for ease of access. If you want to go to the source and a hyperlink has not been provided, you can use the announcements tab here in Hot Copper or the Starpharma Investor's Centre News Archive (for 2016 on).
DEP internal development candidates, with date of first posting.
1. DEP Cabazitaxel, 20 Jan, 2020, 16:52
2. DEP Irinotecan, 25 Jan, 2020, 17:02
3. DEP Gemcitabine, 3 Feb, 2020, 10:13
4. Targeted DEP, 10 Feb, 2020, 10:54
5. DEP Radiopharmaceuticals, 24 Feb, 2020, 9:40
This entry focuses on DEP Docetaxel.
Some initial notes:
1.
@Domesticgod I blame you for the time I spent on this
2. Docetaxel was not the first compound Starpharma tried to conjugate with dendrimers. Work with doxorubicin, oxaliplatin, and insulin were published in early days. Since the company has not yet chosen to move forward with these, I have not covered them.
3. Early company history from 2005 to early 2011 has also not been covered in the interest of providing information about the products Starpharma is actively bringing into or through clinical trials.
4. At the present time, expansions of phase 2 are being completed, both as a monotherapy for various tumour types and in combination with nintedanib for NSCLC. (This is not a prediction of when various aspects of phase 2 will be completed!)
Without further ado, here is DEP docetaxel as it has been brought to us.
201129 June, 2011 (News Release): Docetaxel
nominated as lead candidate in cancer delivery program
- data provided: demonstrated a 2,000 to 8,000-fold improvement in water solubility
- patent filed
- this is the first mention of docetaxelthat I found.
31 Aug, 2011 (Presentation, Macquarie Investor Event):
- Internal program in Drug Delivery (Docetaxel)
- Table provided: Top Ten Injectable Cytotoxins-2009
- Docetaxel 1st, Oxaliplatin, Pemetrexed, Gemcitabine 4th, Pegylated doxorubicin, Irinotecan 6th, Albumin bound paclitaxel, Azacitidine, Paclitaxel, Bendamustine
10 Nov, 2011 (CEO presentation, Annual Meeting):
- Pictures of tumour reduction
- data for three docetaxel formulations in breast cancer model
- comparable efficacy to docetaxel through 30 days
20121 Feb, 2012 (News Release):
Dendrimer-docetaxel formulation shows
improved efficacy in breast cancer model - docetaxel tumour began regrowth by day 60.
- Dendrimer-docetaxel 60% showed no evidence of tumours at 94 days
3 July, 2012 (News Release): Rapid
advancement of drug delivery program- clinical trials expected to commence in 2013
- scaling up docetaxel-dendrimer synthesis for use in further tests toward moving into clinical trials
- initial efficacy results have led to expanding studies of the formulation in diffferent cancer types and at different dosages
- plasma half-life found to be much longer
29 Oct, 2012 (News Release): Starpharma's docetaxel
demonstrates targeted tumour delivery- Starpharma’s (dendrimer) docetaxel formulation resulted in levels of the cancer drug docetaxel in tumour tissue more than 40 times greater than docetaxel
- Evidence of the significant tumour-targeting effect of Starpharma’s dendrimer formulation.
- Further studies are also underway with the dendrimer-docetaxel formulation including investigation of efficacy in various cancer types.
6 Dec, 2012 (
News Release): SPL Docetaxel
superior to Taxotere across multiple cancer types- Breast, prostate, lung and ovarian tumour types were tested.
- The dendrimer-docetaxel formulation resulted in a 26-47% reduction in mean tumour cell survival compared to Taxotere® alone.
- Used technique known as a “hollow fibre inhibition assay” (HFIA) a technique which involves implanting tumour cells into a mouse, then administering an anti-cancer drug to test the drug’s effectiveness. In the present experiment the tumour cells were exposed to the drugs for five days in the mice.
201314 Aug, 2013 (Presentation, Canaccord Genuity Annual Growth Conference):
Proposed short outline of phase 1 trial provided
24 Oct, 2013 (News Release): Starpharma Dendrimer-Docetaxel
eliminates neutropenia17 Dec, 2013 (Shareholder Update):
Phase 1 due to begin early in new year- Another toxicity-reducing benefit attributed to dendrimer-docetaxel is the removal of the detergent – Polysorbate 80 – from its formulation
201423 Jan, 2014 (
News Release):
Phase 1 Dendrimer-Docetaxel clinical trial commences- The trial will be conducted exclusively in Australia, at Nucleus Network's clinical facility at the AMREP/Alfred Hospital initially, with the plan to add 1 to 2 additional sites in the near future.
- Appendix attached with trial details
27 Feb, 2014 (Presentation, ASX Spotlight Event --New York): first time to use DEP terminology
5 June, 2014 (News Release): Presently in the
dose escalation phase- number of patients have now received multiple cycles of therapy with this novel form of improved docetaxel.
- Results so far show very good tolerability for DEP™ docetaxel with no evidence of neutropenia (low white blood cell count).
- Two additional sites, Austin Health/Olivia Newton-John Cancer & Wellness Centre and Royal Brisbane & Women’s Hospital, have recently received ethics approval and are due to commence enrolment shortly.
7 Oct, 2014 (Shareholder Update):
- Despite not having yet reached the maximum tolerated dose (MTD) in the study, a number of patients treated with DEP™ docetaxel have exhibited potential anti-cancer activity with one exhibiting stable disease over many weeks. This is an encouraging sign especially given the doses are lower than the MTD.
- In addition, DEP™ docetaxel has been well tolerated to date. No neutropenia (a low white blood cell count) or hair loss has been observed so far.
- The expansion phase of the study will follow once the MTD is determined. This expansion phase provides opportunity for dosing of multiple patients at the MTD level.
20 Oct, 2014 (
News Release): DEP™ docetaxel shows intended
longer duration and
increased exposure- Preliminary analyses of the pharmacokinetics (PK)of DEP™ docetaxel from the ongoing Phase 1human clinical trial using results from the first cycle of dosing for several patients.
- Beneficial features include
- a very substantially extended duration of exposure
- greatly increased extent of total exposure to drug
- reduced peak levels of drug
- Data provided.
20 Nov, 2014 (CEO presentation, Annual Meeting):
- Phase 1 approaching 50% recruitment
- Not yet at the MTD but a number of patients have exhibited potential anticancer activity (one with stable disease over > 20 weeks)
- comparison chart provided showing DEP docetaxel vs BIND
- Presentation of various advantages of DEP docetaxel vs. Taxotere
201523 March, 2015 (Shareholder Update):
- no neutropenia or hair loss has been observed to date, despite continued dose escalation and some patients receiving as many as 6 cycles of treatment
- 4 sites now involved (one preparing)
30 April, 2015 (
News Release): DEP™ Docetaxel Trial
Dose Exceeds Common Taxotere® Dose Level- no dose limiting toxicities (DLT), including neutropenia
- no reports in the trial of vomiting or hair loss
1 Oct, 2015 (Presentation, OTCQX Life Sciences):
- Phase 1 > 2/3 recruitment
- Interim findings summary included
- A sizable number of patients have exhibited efficacy signals/anticancer activity (one with pancreatic Ca. stable disease over > 20 weeks; prostate, lung, H&N)
29 Oct, 2015 (Shareholder Update);
- Phase 1: a number of patients have now been dosed at the 105 mg/m2 dose level with no cases of neutropenia (Taxotere®’s dose limiting toxicity) or alopecia reported
- Further dose expansion and optimisation is now underway to determine the recommended dose for phase 2. In parallel Starpharma is in active discussions with key opinion leaders locally and internationally to finalise the design and conduct of the phase 2 program.
- It has been identified that DEP® docetaxel’s lack of bone marrow toxicity (neutropenia)may make it an ideal combination agent for immunotherapies and this is potentially also being explored further with various parties.
19 Nov, 2015 (CEO presentation, Annual Meeting):
- Phase 1: Efficacy signals include pancreatic cancer stable disease over > 20 weeks; prostate, lung, head & neck, gastric
- Phase 2: Planning now underway with CROs and key opinion leaders for conduct of Phase 2 Trial including design and indications; clinical trial material manufacture underway
201613 April, 2016 (Shareholder Update): Phase 1: More than 75% of patients have now been recruited
26 Oct, 2016 (
Presentation, PODD Conference):
- Final phase of enrolment underway ; >80% recruited
- Large UK site recently opened will enrich final patient cohort with specific tumour types and facilitate transition to Phase 2
- Efficacy seen in pancreatic (SD* > 20 wks), oesophageal ( SD > 18wks), prostate, lung, H&N, and brain tumours
29 Nov, 2016 (Annual meeting, CEO presentation):
- Phase 1 trial data on limit of side effects and examples of efficacy
- Phase 2: Planning now well advanced including CRO, trial design, KOL's and trial material manufacture, proposed study outlined
201722 Sept, 2017 (
News Release):
Phase 1 results, Phase 2 commences201825 Jan, 2018 (Quarterly Report):
- Phase 2, first patients have received multiple cycles at two hospitals, no neutropenia. Another hospital about to start
30 April, 2018 (Quarterly Report): a
number of patients have been dosed in the
combination study
17 July, 2018 (Quarterly Report):
- 3 sites recruiting, 4th to commence soon
- completed recruitment in the first cohort of patients with lung cancer in the combination study
Oct 17, 2018 (Citi Conference): 4 sites are recruiting
16 Nov, 2018 (
News Release): DEP Docetaxel
outperforms in human pancreatic cancer model- outperformed Abraxane and Gemcitabine, each as monotherapies
- particularly interesting given we also observed stable disease for more than 20 weeks in a pancreatic cancer patient with DEP® docetaxel in our phase 1 trial.
- DEP docetaxel plus Gemcitabine outperformedAbraxane plus Gemcitabine
29 Nov, 2018 (Annual meeting, Chairman address):
- no cases of neutropenia and we continue to see early efficacy signals in a number of patients.
- continue to explore the potential to add value through DEP® docetaxel’s use in combination with other oncology agents, and the potential to include additional indications, if these would add value commercially.
- (CEO presentation):
- Phase 2: no cases of neutropenia and we continue to see early efficacy signals in a number of patients.
- stable disease, tumour shrinkage seen in lung and prostate cancers
- 70% of initial cohort recruited
- investigating other tumour types, includingpancreatic
- combination with nintedanab recruitment is being expanded
201930 Jan, 2019 (Quarterly Report):
Phase 2:Efficacy in a
range of cancers including prostate and lung cancer.27 Feb, 2019 (Interim Report):
- new sites opened to support recruitment.
- Efficacy signals have been observed in a number of patients with a notable lack of bone marrow toxicity and other common side effects including hair-loss, anaphylaxis and oedema
29 April, 2019 (Quarterly Report):
- more than 70% of initial cohort in monotherapy recruited
- Patients in the combination arm also continue to show encouraging efficacy signals and recruitment continues to progress well.
- Recent patent grants include an additional US patent granted for DEP® docetaxel
20 June, 2019 (Presentation: Macquarie Emerging Leaders):
- phase 2 trial...also explore potential combinations
- explore value-adding combinations
July, 2019 (Shareholder Update):
- potential combinations where synergy have already been observed in preclinical studies
28 Aug, 2019 (
News Release):
update on phase 2:
- continue to not see side effects.
- Efficacy in a variety of cancers including prostate and NSCLC.
- Because of efficacy and investigator interest,cohorts have been expanded to explore additional tumour types, including pancreatic.
- Further potential combinations are also being explored following interest from specialist oncologists. This interest stems from DEP® docetaxel’s lack of bone marrow toxicity and impressive performance when combined with other chemotherapeutic agents in preclinical human cancer models.
- data continues to be fed into partnering discussions and has been positively received by potential partners.
21 Nov, 2019 (
Annual meeting, CEO presentation):
Additional interim phase 2 data provided.
- Efficacy seen in several hard to treat cancers (example: cholangiocarcinoma / liver) emphasis on patients all being heavily pretreated with a variety of other treatments.
- recruitment ongoing including patients with selected hard-to-treat tumour types
- combination with nintedanab recruitment is being expanded (not new)
- Other combinations: DEP docetaxel with Gemcitabine targeting pancreatic cancer. To start 1Q, CY2020.
- Combinations with immunotheraphy being explored
- case study: combination with nintedanab
- phase 2 completion estimated 1H, CY 2020.
- In spoken remarks, combination with Gemcitabine will probably extend longer.
- CEO verbal comments
- combination with Gemcitabine will include use in first-line treatment in some patients
202029 Jan, 2020 (Quarterly Report):
- Six sites in the UK are now recruiting patients (not new ..all six were named in the 2019 Annual meeting CEO presentation)
If you made it this far, wow!This will be updated occasionally.
