Dr. Joshua Lederberg

Apt. 115
/ 1230 York Avenue
cL New York, NY 16021-6389
Report on visit to Quidel 8/28/87 SEP 3 1987

From: Joshua Lederberg
To: David Katz, Joe Stemler, Steven Coutts
I very much enjoyed my visit, and thank you for your hospitality.

Leaving out some of the compliments, I extract what I reported back to JDW,Inc.

1. They have just appointed Stephen Coutts to bolster their R&D effort. He seems just
superb!

2. The SFA project has the potential of becoming one of the major applications of R-DNA
technology: the stakes are a market measured in units of $100MM (or more!). Inevitably the
odds are rather long too (or, rather, very hard to estimate.) If SFA were a sure thing, the field
would be crowded with competitors. (The only visible one is Ishizaka at Johns Hopkins, who
is affiliated with DNAx -- we don’t know much about where they are at.)

3. SFA has been cloned (they did a superb job of that), and this has given them a source of
ample material for further trials. They have interesting biological activities in vitro, and a
50% suppression of IgE production in the mouse. Nature is not always so kind in offering
activity of human lymphokins in animal models. David Katz is eager to push ahead with
clinical trials in the human, and this is a strategy that may well be supportable. I expressed
some concerns that they had not exhausted all they could do in the mouse -- €.g. to attempt a
recognizable "clinical" amelioration of allergy in the mouse; also to set up a less extreme
antigenic stress that might allow SFA to exhibit more complete suppression of of IgE
production. David seems to feel this is unnecessary (and that this assay would be criticized
precisely because a more modest IgE reaction was being targetted.) Besides the scientific
argument, they may run into trouble with an IRB or the FDA in getting approval for an IND
if they have not exhausted all the feasible and relevant animal tests. It would be unfortunate
to lose precious time by not anticipating these potential roadblocks.

4. We also discussed, and Steve agreed, that FDA will demand the complete sequence of
SFA to be matched against their cloned material prior to any NDA (and possibly prior to any
extensive IND trials). The first 20 or so N-terminal amino acids were sequenced, and this
was the basis of the probe used to extract the c-DNA used in cloning. At least a peptide map
might help to verify the authenticity of the sequence.

5. We also discussed the GL-nucleoside immunosuppression of anti-nuclear antibodies for
use in SLE. They need to verify that the majority of total auto-immunoglobulin is antinuclear
for it to be plausible that it will be clinically useful. Other auto-immune diseases (thyroiditis,
myasthenia gravis, auto-immune male infertility) might be better candidates, with simpler and
better understood provocative antigens. The latter is one of the commonest causes of
infertility; some women also have anti-sperm antibodies secreted in cervical mucus. The
antibodies are directed against flagella.
6. On the whole, QUIDEL has a splendid scientific group, and Steve’s recruitment should
give them a special edge in working out strategies for the most effective implementation of
the R&D cycle, and bringing SFA to the market. I have to repeat that the stakes and the
technical and business risks are both very large.

7. Frank Austin is in general concurrence with the above.

Joshua Lederberg

cc: F. Austen