I am a bit late in providing the below bullet point summary of the Conference Call (as suggested by BioInfo & Staccani), but here it is nonetheless.
I might have easily missed some stuff, since I was trying to listen, comprehend, and make notes all at once, and I am not in the medical field at all.
(Note: I had sent in a bunch of questions on the CC link this morning, including some of the questions of posters here on iHub, and was pleased that LP did address several of these questions).
May 27, 2014 conference call. Linda Powers.
We have a long way to go. Most patients are at least half way through Phase I treatments. Quite encouraging so far.
Response to naysayers:
1. Just continue to make strong progress
2. Quite a bit more will be coming out in the coming months
3. NWBO will continue to set the record straight if the naysayers are too far out of line, and the company intends to correct misinformation.
Phase I: finish in 2015? I was not clear whether LP implied this should occur sooner.
LP indicated it is incorrect that the trial may need to keep stopping based on safety issues.
Patients that are being treated have very advanced stages of aggressive cancer that has metastasized and currently they have no effective treatment options. All they have is palliative options.
To see over 50% of the 19 patients responding is quite encouraging, especially since they are only half-way through their treatment. And, in comparison:
Checkpoint Inhibitor drugs, which are being mentioned recently as promising, are seeing only a 25% response rate when used as single agent, and still only around 40% response rate when combined with other treatment/drug.
Putting the trial itself into context: this 60 patient Phase I/II trial is actually unusually large, especially in a “1st in man” trial.
More typical would be say 12 to 20 patient trial size.
Safety is the primary focus for Phase I, so to see the early indications of efficacy that have been seen is like “frosting on the cake”.
It has been shown that DCVax Direct is being very well tolerated by the patients. All dose levels have been very well tolerated (indicating good safety).
NWBO has rented a very large booth at ASCO and intends to provide even more info at this booth.
Most of the patients have experienced a fever lasting 1 day, or sometimes 2 days, after each injection. Which is typical and not unexpected. Most fevers were below 39 degrees C, and thus a minor fever and some just took some tylenol to combat fever symptoms.
No other adverse effects to date, although one patient did experience a couple hours of nausea on 1 occasion. Some pain or discomfort was mentioned related to the needle prick, and it was noted to be similar to discomfort of a biopsy needle application.
LP noted similarities in safety & adverse effects to what they have seen with DCVax-L.
Doctors have commented that treating patients with DCVax-Direct was very simple and practical and easy to administer. They expressed that it would be easy to incorporate in Routine Medical Practice.
All patients were treated with one of 3 types of image guidance (Ultra-sound, MRI & ..???..).
Degree to which the early results might be indicative of longer term results?
The results so far have been consistent with the biology and platform technology and with what the company has seen in lead product DCVax-L. At this time it is not yet possible to predict whether the future data might be better or worse.
Dose levels: 3 current dose levels:
• Low = 2 million cells
• Medium = 6 million cells
• High = 16 million cells
Standard dose escalation. “3x3”: 3 patients at each dose level.
Low & medium dose levels have been completed (for the 19?).
High dose level … mostly completed.
So far there is no pattern whether patients may do better/worse depending on dose level.
Not surprising, and consistent based on immunology & based on experience with –L.
Screenings for Phase II. Chosen indication?
NWBO will proceed into Phase II after Phase I has finished. Phase I is currently finishing enrollment.
Therefor NW is not yet enrolling for Phase II.
NW has not yet chosen which cancer type will be involved with Phase II.
It is too early to have good idea about patterns & which cancer type might respond best.
NW has already seen positive results in several of the multiple (very diverse) cancer types, including: sarcomas, pancreatic (being 1 of the worst, with mestast, similar to what Steve Jobs had) and colon (colectoral).
These are just examples so far. Lots more to be learned.
This is “1st in man” based on injections into a single tumor.
Two effects being seen: localized in the tumor which was injected (good results), and systemic … mobilized… in tumors which were not injected.
LP expressed they were surprised to see the systemic effects so early, with patients that are only half-way through their treatment. They were not anticipating seeing this.
Necrosis …. T-cell death, and accumulation of immune cells coming to the site.
When might NW pursue multiple injections into multiple tumors? Phase II? Phase III?
Some tumors very large (up to 17 cm).
NW expects to start down this path “Quite Soon, indeed”.
It would be a separate data set. Not commingled with current data. Would proceed with a new batch of patients. Same protocol? Same IND? IMD?
Someone asked whether Phase II might also start with a “slow period”. Answer: No. Especially due to the terrific safety profile to date.
What constitutes current Standard of Care? Answer: there is no SoC for the patients being treated in this trial. These patients have cancers that are currently deemed beyond any curative treatment and just being provided with palliative care today.
LP spoke about the type/quantity of immune cells found in the tumor, and was quite excited. Overall immune system. Multiple types, including CD4 (“helper”) and CD8 t-cells.
Macrophages?
Major response by t-cells, and a mixture of various cells.
Tumor shrinkage seen? Keep in mind that most only had 3 or 4 treatments, and already tumor shrinkage of up to 28% was seen, which is very significant at this early stage.
Also seen various cases where the tumor was enlarged, in part by necrosis and in part due to accruing immune cells. As more is recently becoming recognized & understood about this. It is expected that these enlarged tumors will collapse later on.
Manufacturing = “Mission Critical”. NW versus competition.
NW has given manufacturing their intense focus during entire existence of over 10 years.
Various critical stages of manufacturing have been automated (with patents nicely in place/issued).
High purity.
Working on further automation.
NW benefitted from their experience with DCVax-L (honing fo manufacturing reached).
NW has been very pro-active in pursuing all possible regulatory pathways. In USA and in Europe. In Europe there appears to especially be various pathway options, including conditional, and more recently also includes “Adoptive Licensing” (which is a new pathway that NW is looking into).
Right to Try (ie: in Colorado).
NW has always been very supportive in looking to provide Early Access. NW is watching this development. Looking to see how it might fit (including fitting with FDA). Too early to tell what might come of this.
Improved Quality of Life?
This has been seen in all stabilized patients (those whom have not progressed). Patient comments have included that they are “feeling better than in any time they can remember”. Keep in mind these patients have been through a lot prior to getting to this trial/treatment.
Current Enrollment?
All 36 slots filled!
Enrollment includes Eligibility Screening PLUS product has been made.
In a small number of patients: their immune cells were found to be not good enough anymore (to produce product?).
23 Enrolled (19 patients with 3 or more treatments, plus 4 patients with 1 or 2 treatments)
7 patients with 1st injection to occur this week or next week
Remaining 6 patients: blood draw still to take place.
Anticipating all above 36 patients to be “fully enrolled” by approximately end-June.
Things started to occur very rapidly once the trial was no longer restricted.
There are so many patients with inoperable cancers with no SoC. NW has been flooded with prospective patients for this trial. There has been a waiting list for available slots.
Even some patients that have just recently enrolled are already seeing rapid response.
Different results being seen based on how “old” the cancer diagnosis is?
Great question.
NW is actively exploring this question.
NW is reviewing medical histories.
So far, NW has not seen any particular patterns.
Quite encouraging that they are still seeing a good response with –Direct in patients with longstanding and very advanced cancers.
Effect of chemo etc on patients’ immune system and ability to still respond to -Direct? In some cases the patients are indeed “terribly broken” by the time they have gone through many, many prior treatment options.
Dosage. All 19 at same dose? Incremental later?
Low, medium and high doses: positive across the board.
Once a particular patient is started at a certain dose, then this patient will only receive this particular dose level for all remaining treatments.
Who does the review of the data?
In all cases, this is done by the team which includes NWBio, both MD Anderson facilities plus the CRO. In every case this team reviews every piece of data and all members of this team come to a conclusion/agreement on the meaning of each piece of data.
All senior management of NWBO will be at ASCO.
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