Personalized genomics inflection point

One of the world’s fastest accelerating technologies is that of genomic sequencing. The first whole human genome (6 billion base pairs) was sequenced at a cost of $3b and was completed in 2003. The current cost is $20,000 for researchers (Complete Genomics) and $48,000 for consumers (with Illumina’s EveryGenome program). Leading third-generation sequencing company Pacific Biosciences affirmed at the Cold Spring Harbor Laboratory Personal Genomes meeting September 14-17, 2009 that the company has 12 prototype instruments in operation and continues to be on track for ~$100 (“the cost of a nice dinner”) whole human genome sequencing to be commercially available in the second half of 2010. NimbleGen indicated that they may have a $2,000 exome sequencer available in 2010.

In a challenging venture capital climate, Pacific Biosciences was able to close an additional $68m round in financing on August 12, 2009. Leading commercial sequencer Complete Genomics was also notable in closing a $45m D round on August 24, 2009. The company has sequenced 14 whole human genomes to date, and hopes to sequence exponentially more, 10,000, in 2010 at a minimum cost of $5,000 per genome.

Viability of DTC genomics sector
Where the genomics technology sector has rosy prognostications, the direct-to-consumer personalized genomics market has volatility. Events in the last several months have led to questions of the sector’s viability with upheavals at the three leading companies, 23andme (“Avey Leaves 23andMe to Start Alzheimer's Research Foundation Using DTC Genomics Firm's Platform"), deCODEme (“deCODE close to broke” – Augusty 11, 2009) and Navigenics (“Navigenics Names Jonathan Lord, MD to Serve as President and Chief Executive Officer” April 7, 2009). Absent innovation, DTC genomics companies are a “window business” in the sense that the window for their current offerings may only be open for a short time with the advent of whole human genome sequencing and standardized public multi-SNP condition interpretation tools.

Figure 1. Direct-to-Consumer Genomics Offerings: ongoing price declines (Chart PDF)

As depicted in Figure 1, there are three types of Direct-to-Consumer (DTC) genomics offerings currently available directly to individuals: one-off SNP (single nucleotide polymorphism) tests for specific conditions and paternity tests, multi-SNP risk assessment tests mapping several SNPs to dozens of disease conditions and whole human genome sequencing assessing hundreds of disease risks. The five companies offering multi-SNP risk assessments are: 23andme ($399 for 111 conditions), deCODEme (42 conditions for $985), Navigenics (28 conditions for $999), Gene Essence (84 conditions for $1,195) and Pathway Genomics (77 conditions for $249). 23andme, deCODEme and Navigenics are the most transparent, disclosing the specific SNPs, research references and risk assessment methodologies for their tests, Gene Essence discloses SNPs and Pathway Genomics does not disclose anything. A detailed condition and SNP analysis is here.

Slow DTC genomics adoption
DTC genomics has had slow adoption so far for several reasons, first, there has been very little marketing, few consumers know of the availability and value proposition of DTC genomics services. Second, since automated tools are not yet available, many people are not interested in preventively managing their health, and may still perceive it to be in the responsibility and domain of health care professionals. Third, the conventional but incorrect view is that genetic information is already known (from family history), negative and deterministic. Fourth, as initially pointed out by ExperimentalMan David Ewing Duncan, there are conflicting interpretations from DTC services for the same conditions such as heart attack. This is because the scientific community has little knowledge and agreement yet regarding multi-SNP conditions. DTC companies are looking at different SNPs, assigning different quantitative risk values and employing differing estimates of overall population averages which all contribute to heterogeneous interpretations of risk for the same condition.

VC guide to anti-aging biotechnology investing

Several promising startup companies focused on the nascent but obviously significant and growing anti-aging biotechnology space were present or discussed with interest at the recent SENS4 (Strategies for Engineered Negligible Senescence) conference in Cambridge, U.K., September 3rd – 7th, 2009 (program) (full conference report).

1. Epeius Biotechnologies, San Marino, CA, USA: Rexin-G, a tumor-targeted injectable gene delivery system
2. FoldRx, Cambridge, MA, USA: small molecule therapeutics to treat protein misfolding diseases, and bind and clear undesired molecules
3. Gencia Corporation, Charlottesville, VA, USA: mitochondrial DNA rejuvenation using the rhTFAM (recombinant-human mitochondrial transcription factor A) protein
4. Genscient, Fountain Valley, CA, USA: novel chronic disease therapeutics by combining genomics and selective screening (a large Alzheimer’s Disease genetic study is in progress with Kronos and TGen)
5. Knome, Cambridge, MA, USA: whole human genome sequencing (consumer offering)
6. Neotropix, Malvern, PA, USA: oncolytic viruses for the treatment of solid tumors
7. Pentraxin Therapeutics Ltd, London, UK: small molecule drug CPHPC specifically targeting SAP (serum form of amyloid P) and removing it from the blood and brains of patients with Alzheimer’s Disease
8. Repeat Diagnostics, Vancouver, BC, Canada: telomere length measurement for total lymphocyte and granulocyte populations (consumer offering)
9. Retrotope, Los Altos Hills, CA, USA: using isotope effect to slow down damage pathways and control metabolic processes associated with oxidative stress
10. StemCor Systems, Inc., Menlo Park, CA, USA: bone marrow harvesting system
11. T.A. Sciences, New York, NY, USA: telomerase activation via the single molecule TA-65, licensed from Geron Corporation (consumer offering)
12. TriStem Corporation, London, UK: retrodifferentiation technology to create stem cells from mature adult cells

Angel investors drive innovation

The Center for Venture Research at the University of New Hampshire reported that in 2007, angels invested almost as much as venture capitalists in startup companies, $26.0 billion vs. $29.4 billion. Focused on seed and startup stage financings, angels invested in far more firms, 57,120 vs. 3,813 for venture capitalists. Angel investment growth was flat in 2007 vs. 2006 while venture capital investment grew 11%. San Francisco Bay Area angel investors comprised 10% of total angel investment activity. As with venture capital, the top four categories of angel investment in order were software, healthcare, biotech and energy.

Angel investing was once a solitary activity driven by personal networks, the practice has been formalizing in the last several years and there are now over 150 angel investor groups in the U.S. and Canada. The groups typically meet monthly where 3-6 pre-screened companies present to members. Angel investors are not disengaged retirees, 80% continue to be actively involved in the business world. Cleantech and even social venture capital are starting to be interest areas for angel investors.

Angel investors are a critical component of the entrepreneurial ecosystem and should be encouraged and sponsored by communities trying to establish a more innovative environment. For startups, angels can be an important resource for funding, feedback, contacts and exposure. The contribution and impact of angel investors can be expected to grow.