Anger

I was asked to be interviewed by Heather Van Epps for an article on anger when dealing with cancer diagnosis in CURE magazine. She is the author of the linked article on another "good cancer". She is obviously a sharp and sensitive writer and I am sorry our schedules prevented us from connecting. I would have liked to have been part of her research.

Oh, well.

Here is what I would have said if asked:

Anger is an appropriate and often helpful tool if it motivates you to push for answers. It means that you care, that you are involved, that you don't just blindly accept the standard options. It quickly becomes destructive if it drains your energy, diverts your purpose, or alienates your care team.

This is what I posted in August 2010. Most of it from the words of the great medieval physician, philosopher, rationalist, and theologian, Moses Maimonides.

The Rambam said

He should not let loose the reins of anger nor let passion gain mastery over him, for all passions are evil; but, on the contrary, he should guard against them as far as this lies within the capacity of man. Sometimes, with regard to some people, he should be merciful and gracious, not out of mere compassion and pity, but in accordance with what is fitting.

In the treatise on Character Traits, he admits that there may be times when it is necessary for a person to show anger, but insists that inwardly she should remain completely tranquil.

What happened to balance and the idea of mental health? The answer is that while they are still valuable, they are not ends in themselves. Throughout his rabbinic and philosophic works, Maimonides insists (MT 1, Character Traits, 3.1) that it is impossible to love God and achieve the highest levels of concentration if one is sick, undisciplined, or living in fear of bodily harm. But in the end, moral perfection is only a necessary condition for intellectual perfection.

Stolen from http://plato.stanford.edu/entries/maimonides/

Anger is nowhere. I need to meditate more and stay calmer and stronger, even when confronting the negative and even the evil.

And I will.

Why did I change? Maybe it's just me trying to be contrarian and give some breathing room to the imperfections in the readers and in myself.

Pharmacyclics: When The Power Of A Pipeline Overshadows The Market's Influence On Value

From Seeking Alpha

Maybe it is still a buy? I'm thinking of putting my money where leukemia is.

Pharmacyclic’s (PCYC) story is one of a few where the power of pipeline drugs has overshadowed the stock market’s technical influence on a biotech company's value. In other words, in the case of Pharmacyclics, investors should be looking for something extraordinary in the firm’s pipeline, in its choices of its programs, in its plans and strategies in developing its pipeline products and its capability of executing its plans and reaching its goals. Pharmacyclics’ Bruton’s tyrosine Kinase (BTK) inhibitor PCI-32765 therapeutic is unique. In December 2011, Pharmacyclics was granted U.S. patent that testifies to the drug’s exceptionality. It is, indeed, the first irreversible inhibitor in the BTK zone.

BTK is an important cell-signaling enzyme found in blood cells including B-cells. B-cell activation is driven by the B-cell receptor (BCR). Pharmacyclics’ PCI-32765 target BTK is a crucial part of the BCR signaling pathway, believed to promote cell proliferation, adhesion, and survival many types of B-cell cancers. So, by blocking BTK, PCI-32765 halts proliferation, disrupts tumor cell adhesion, and causes malignant B-cells apoptosis (cell death). Inhibition of BTK also blocks the recruitment and function of other immune cells including monocytes, macrophages and mast cells. Studies in mice have shown that orally-dosed PCI-32765 reduces the level of circulating auto-antibodies and can reverse the course of arthritis. PCI-32765 also inhibited production and the development of kidney disease in a mouse model of systemic lupus erythematosus ((SLE).

Therefore, PCI-32765 inhibition of BTK is expected to treat various human diseases associated with the abnormal activation of B-cells, including B-cell cancers, autoimmune diseases and other inflammatory diseases. PCI-32765 is orally active, selective and irreversible small molecule. It is in fact in clinical trials for B-cell cancers (chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma, diffuse large B-cell lymphoma (DLBCL) and multiple myeloma).

More important than hypothesizing based on literature, or relying on early preclinical observations, we preferred to wait for a clinical confirmation of the safety and efficacy of PCI-32765. We obtained the good news at the 53rd American Society of Hematology (Ash) Annual Meeting in December 2011. At that meeting, the director of Mantle Cell Lymphoma (MCL) Program at MD Anderson Cancer Center, University of Texas presented data demonstrating that PCI-32765 had a high rate of overall response as a single therapy in patients with relapsed or refractory mantle cell lymphoma, including patients that had been previously treated with bortezomib (Velcade®). The overall response rate was 71% in Velcade-naive patients and 65% in Velcade-exposed patients. At the time of this analysis 89% of responding patients have ongoing responses and the median follow-up was at 3.7 months. The most common adverse events were Grade 1 (mild) or 2 (moderate) fatigue, diarrhea and nausea. Three patients discontinued the study due to adverse events regardless of causality. Overall, these data supported Phase III evaluation of PCI-32765 as a single agent in patients previously treated for MCL.

Other presentations in the Ash meeting provided significant insight on the efficacy and safety of PCI-32765 in chronic lymphocytic leukemia and activated B-cell subtype diffuse large B-cell lymphoma. We found the results sufficient to confirm PCI-32765 therapeutic potential and validate Bruton’s tyrosine Kinase as a superior target for the treatment of the B-Cell cancers.

The performance of PCI-32765 in Phase II trials attracted many firms to partner with Pharmacyclics on the drug but PCYC preferred Janssen Pharmaceutical of Johnson & Johnson (JNJ) as its partner. The terms of the partnership agreement, including the $150 upfront payment, the additional $825 million milestone payments, the percentage of the contribution to the cost of development (Pharmacyclics 40% and Janssen 60%) while equally splitting the profits (or losses) worldwid,e has offered evidence of the importance of what Pharmacyclics has in hand.

Again we say that Pharmacyclic's uninterrupted stock rally is not based on market speculations, but on the mere refreshing reality of the firm’s pipeline. Bruton’s tyrosine Kinase (BTK) inhibitor drug PCI-32765 is the first irreversible inhibitor to show in the BTK domaine and we have reasons to believe that its oral pan-histone deacetylases (HDAC) inhibitor drug PCI-24781 (abexinostat hydrochloride) could be important among a few molecules in the epigenomics zone, contributing to the ongoing process of transforming basic science into applied science. We will tackle this program in a future article about Pharmacyclics

Both drugs and their targets qualify Pharmacyclics as candidate for takeover by large-pocketed pharmaceutical or biotech companies.

Simply said, Pharmacyclics has made huge steps forwards towards advancing the treatments of cancers and chronic debilitating diseases. Is this not what the biotechnology industry is all about?

Lost Again

I am a bit lost these days.

I am in the trial, this trial that I pushed so hard to nab a precious slot and cajoled the insurance to cover an expensive out of state option.

Done deal.

Over the last few years when sadly it became all so clear that my transplant was not going to be my way out of the cancer dance, we have been waiting for just such a third chance, waiting for just such a trial. We have been saving up and preparing as best we could to manage all the out of pocket expenses and emotional stresses of flying back and forth and staying warm and dry in a city with a hard winter and sticking with my raw vegan organic diet outside the comfortable crunchiness of California.

I have read and scanned thousands of CLL articles and spoken with hundreds of fellow patients and scores of clinicians and researchers waiting for a new pathway out. In this case it is a pathway that is at once novel however you deconstruct it, be it molecular or therapeutic or modal.

Molecular: It is small molecule, small enough to get through the gut and into the cell unscathed, so you can take it in pill form. No infusions. It's not really even chemo. It doesn't kill, but blocks proliferation. Birth control for cancer.

Therapeutic: It's therapeutic response rate is near an amazing 90% in difficult to treat relapsed populations. And the longer you stay on it, the better the respond rate. Toxicities are low too.

Modal: It doesn't wipe out the cancer or even knock it back to undetectable levels, at least not at first. It may not even get you into remission. It just slows it down, it reaches a compromise with the nasty clone, so we all get along and live in harmony hopefully for a long long time

Is this a sea change in the molecular, therapeutic and modal approach to CLL? I am one of the "subjects" that should help answer those questions. I am betting yes and putting my body and my money where my mouth and pen is.

I got what I wanted. More than I could have dreamed of less than year ago when Dr. Furman when presented the preliminary data from his first in human trial of this new medicine, PCI-32765.

So why am I so lost?

Lack of clear purpose? A schedule full of so many permutations and combinations that my math and logic skills fail me? A domino effect that this decision effects that decision that effects the next and so and so on? Decision fatigue with so many mundane and critical choices shuffling around in my tired head for attention?

Maybe it is because my flight and lodging plans are less clear now than a week ago, but that's because of exciting new possible options?

Maybe it's the realization that I have lived with the fantasy for so long and now I am opening my body and soul to the reality that I am going forward? I am really doing this. The surrender of all that is possible in every moment to hard fact of the done decision.

I am not wavering. I am not panicked or depressed or even anxious.

I am just a little lost.

I will simply live here with this disorientation because I know it will be just fine. It is not that I am expecting some divine intervention or even an inspired secular EUREKA moment. Unlike one of my hero's Dr. Terry Hamblin, I am not one to "trust in G-d and think laterally". At least not the trust G-d part

Rather I know it will be fine because this "lostness" is ephemeral. It's real but of no consequence and is made of nothing. It is only a learning opportunity, not a place to hang out. I need to examine it and then it evaporates on its own.

It will definitely be gone by the time I touch down in Columbus in my winter coat with my wife by my side and my green tea and juicer in my baggage.

It will probably be gone much sooner.

This writing speeds the process. I am feeling less lost already.

No worries. Struggles, yes, worries, no.

I'm in.

First step was a quick trip to Columbus, Ohio to meet the trial team at OSU and see if there was a fit between what treatment I needed and what PCI-32765 or similar trials or treatments they could offer.

Dr. Byrd dutifully told me of my conventional treatment options that he would recommend if I wanted an existing conventional treatment. He recommended against FCR for me due my ITP, but BR would make sense. I declined his obligatory offering of all the options and focused in the real reason for my visit, the chance to get some PCI-32765.

We quickly dismissed the shorter more convenient diet trial, not because it called for measuring the absorption of the oral medicine, PCI-32765 after either skipping breakfast entirely or a Jewish vegan's nightmare fatty breakfast of eggs and bacon (or the kosher vegan equivalent if there is such a thing), but because the trial was FDA mandated and as such, would be much less flexible.

Instead, we zeroed in the investigator initiated third and final cohort of trial of PCI-32765 + O (Clinical Trial NCT01217749).

Then they had to make sure I fit all the inclusion and none of the exclusion criteria. I did. I was in because my B cells had recovered their CD20 dim status (necessary for the ofatumamab to work) and they counted the rituximab for my ITP as one of my two failed therapies. And there was no exclusion for a prior transplant.

Next it was critical that I understood all the risks inherent in an early phase trial. No assumption that because I was a doctor, they could gloss over the details. They spelt them all out- infections, subdural hematomas (bleeding into the brain), diarrhea, GERD, rashes and more.

Undeterred, I said yes. They said yes. Consent done.

Now would the insurance say yes to an expensive out of state trial? They have to cover in state trials, but out of state coverage is more problematic.

After a few paperwork and fax snafus, my angel from Blue Shield very quickly told me it was a go.

Now my life is on hold until I get my schedule for the next 8-12 weeks of weekly appointments at OSU. That should come soon.

In the meantime, I have temporary lodging lined up, I know of some of the nearby synagogues, and I have found what little organic vegan food (ironical much of it is imported from California) there is to find in wintery Ohio. A dear friend who teaches at OSU has made social introductions to fellow professors for us. We have a map of the regional parks to explore, and my computers are fit and ready to travel so I can research and write up a storm while in Ohio. I have friends to commissirate with who are already getting care in trials for their CLL at OSU.

We have someone to house sit and collect the mail. I still need to book the flights, rent a car, plan my frequent return visits here to see my patients, pat the cat, teach, pay my taxes, and get my IVig and arrange a few hundred small things.

It is all so exciting and promising.

It's time to wait and hurry up.

It's time to celebrate another shot at a long healthy life, even with cancer.

I am so lucky, so blessed. I must use this gift to make a difference. I promise I will.

I move forward with deep humility and gratitude, more than a pinch of trepidation and a freight train of wide eyed optimism.

Spiritual Discrimination

Spiritual Discrimination « Daat Elyon

http://daatelyon.org/2012/02/spiritual-discrimination/

Februray 17, 2012

Every morning, we begin our day with the following prayer:

“Blessed are You, O Lord our God, Who gives the rooster understanding to distinguish between day and night.”

The attribute of discrimination is a great blessing. Discrimination is a power of the mind. It is the capacity to look at any situation and analyze its component parts – to distinguish between day and night, right and wrong, good and bad, true and false.

The ability to discriminate is one of the distinctive characteristics of a human being. It is the key to our growth and evolution. It is only by discriminating that we can learn to make conscious choices in our life. As the Dhammapada states:

“A wise man calmly considers what is right and what is wrong, and faces different opinions with truth, non-violence, and peace.” ^[1]

Discrimination is essential in our relationship with others. We live in a world of appearances where the outer façade often belies the person underneath. Sometimes a person with a beautiful exterior is ugly inside, while an individual who outwardly looks ragged and unappealing is inwardly shining with light. It is important for the spiritual aspirant to learn to discriminate between a saintly appearance and true holiness.

Discrimination also plays a role in determining the activities in which we invest our energies and the surroundings in which we spend our time. Not all situations that are pleasant are spiritually beneficial. Some situations that appear congenial on the surface may have a negative spiritual influence. Some of the groups which call themselves spiritual actually have nothing to do with the life of the Spirit.

Our inner growth lies in learning to differentiate between platitudes and real spiritual truths, between sentimentality and true compassion; between the attitude that says “everything is the same” and an inclusive consciousness that embraces all of humankind.

People often become confused when trying to reconcile the spiritual truth that “all is one” with the harsh reality of our physical world. When asked about this conflict, Annamalai Swami, a disciple of Sri Ramana Maharshi, gave his students the following analogy:

“I once went for a walk near the housing board buildings. There was a sewage trench on one side of the building. I could smell the stench of the sewage even though I was a long way away. I stayed away from it because I didn’t want to be nauseated by the bad smell.

“In circumstances such as these you don’t say, ‘All is one. Everything is the Self,’ and paddle through the sewage. The knowledge ‘everything is the Self’ may be there, but that doesn’t mean that you have to put yourself in dangerous or health-threatening places.

“When you have become one with the Self, a great power takes you over and runs your life for you…If you are not in this state, then use your discrimination wisely. You can choose to sit in a flower garden and enjoy the scent of the blooms, or you can go down to that trench I told you about and make yourself sick by inhaling the fumes there.” ^[2]

A developed sense of discrimination is an essential part of the equipment of any serious spiritual seeker, without it all of our efforts may be in vain. Positive intentions and a desire to be good are not enough; we must also be able to see ourselves, and the world around us, with clarity. Otherwise, God will not take the chance of putting His powerful energies into our hands.

There is yet another level to the process of discrimination. In the spiritual life we seek to know not only what is good and bad, but also what is real and unreal; what is the Self and the “not self”. Here, discrimination is more than a capacity of the mind; it is a property of the soul.

Through the intuition, we learn to discriminate when the higher or true Self is at work and when the lower or “not self” is pushing itself forward; to differentiate between our own desires and God’s Will. People often believe that they are serving the Will of God when really they are only fulfilling their own wishes. It is a natural tendency to assume that what we want is what God wants as well. It is rarely the case that this is so. God’s plans for us often demand that we undertake actions that we do not wish to pursue. It is a real test of our humility when we need to put aside our own desires and accept what God wills instead.

In this case, discrimination means an honest appraisal of our abilities combined with a rock bottom assessment of where we are in our spiritual journey. It means differentiating between dreams and reality. It demands a willingness to sacrifice our illusions in return for a real job for God.

The attribute of discrimination has a great transforming power. Rebbe Ephraim of Sadilkov, the grandson of the Baal Shem, teaches that a person who has discrimination is able to completely change his nature:

“For the form must be like the one who made it: Just like the Maker of All created the natural world through wisdom, as it is written, ‘you made them all with wisdom’ [Psalm 104:24]… so a man of discrimination and true wisdom can create for himself a whole new nature…

“For example, if he was born with an angry and lustful nature, if he is a man of discrimination, he can change his nature and conquer his anger… as is written in Proverbs: ‘The discrimination of a man makes him slow to anger.’” (19:11) ^[3]

Rebbe Ephraim believed that the transforming power of the attribute of discrimination reaches beyond our own individual selves. He teaches that a tzaddik (enlightened soul) who has bound his mind to God can “change all natures – both physically and spiritually – for the good and for a blessing.”

The discrimination of a tzaddik has the power to influence others and help them to break free from their attachment to wishful thinking and illusion. By shining the light of commonsense into a situation, he shatters superstitious practices, ideas and beliefs. When his clear radiance is cast on that which is evil, it exposes the ugliness and lifelessness that lies at its core. And when it shines on that which is good, it reveals the vitality and inner beauty for all to see.

A holy person is the very embodiment of truth. Contact with a holy person purifies and uplifts the sight of those around him or her. Their minds become loosened from material confusion. They see the world with a new clarity. They begin to understand the true purpose of their existence, to intuit what is real and what is not.

Sri Ramakrishna used to tell his householder devotees:

Haven’t you seen the trees on the footpath along a street? They are fenced around as long as they are very young, otherwise cattle destroy them. But there is no longer any need of fences when their trunks grow thick and strong. Then they won’t break even if an elephant is tied to them. Just so, there will be no need for you to worry and fear if you make your mind strong as a thick tree-trunk. First of all try to acquire discrimination. Break the jackfruit open only after you have rubbed your hands with oil, then its sticky milk won’t smear them.” ^[4]

The faculty of discrimination is an essential element of our spiritual equipment. It instills within us the higher awareness that we need in order to live upon this material plane. It enables us to pursue the lofty life of the Spirit, while immersed in the tumultuous existence of this physical world.

Copyright © 2011, by Yoel Glick

Important discriminating essay. But I want more.

You say: "Through the intuition, we learn to discriminate when the higher or true Self is at work and when the lower or “not self” is pushing itself forward; to differentiate between our own desires and God’s Will. People often believe that they are serving the Will of God when really they are only fulfilling their own wishes."

That is the rub. How can you tell? From the mundane (Is the urge to skip exercise today my body saying you need to rest or is just being lazy?) to the profound (Will giving more charity to help those in need help them get going again or will it foster dependence?) What urges are divine and merciful and just are well disguised self serving drives?

How do you tell?

How we decide anything spiritual or material is where I am hanging out these days.

How do we sort it all out?

Pharmacyclics, Inc.

As the wise man said, follow the money! I sure am. Almost a billion dollars. 975 million to be precise.

I was not smart enough to invest in the company when I saw this coming, but I was smart enough to jump aboard one of the last trials before the registration trials for FDA approval begin. Those will be double blinded so there is only a 50-50 chance of getting the drug, and more importantly, they almost always exclude transplant patients such as yours truly.

So it is this trial or maybe nothing for a few years. I didn't want to miss that boat to a safe harbor. My trial is in red in their financial report.

But do you think I really missed the boat to buy the stock? It's value has doubled over the last few weeks, but does it still have room to rise?.

From PRNewswire

SUNNYVALE, Calif., Feb. 9, 2012 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) today reported financial results and recent developments for its fiscal second quarter ended December 31, 2011.

Financial Results for Second Quarter Ended December 31, 2011

The non-GAAP (Generally Accepted Accounting Principles) net income reported for the fiscal quarter ended December 31, 2011was $58.6 million, or $0.82 diluted earnings per share. This compares with a non-GAAP net loss of $6.1 million, or $0.10 loss per share, for the fiscal quarter ended December 31, 2010. See "Use of Non-GAAP Financial Measures" below for a description of our Non-GAAP measures. Reconciliation between certain GAAP and non-GAAP measures is provided at the end of this press release.

The GAAP net income for the fiscal quarter ended December 31, 2011 was $56.3 million, or $0.78 diluted earnings per share. This compares with a GAAP net loss of $7.5 million, or $0.13 loss per share for the fiscal quarter ended December 31, 2010.

At December 31, 2011, the company had cash, cash equivalents and marketable securities of $240.3 million, which compares with $112.3 million at June 30, 2011.

As previously announced on December 8, 2011, the Company entered into a worldwide collaboration with Janssen Biotech, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to develop and commercialize PCI-32765, a novel, oral, first-in-class Bruton's Tyrosine Kinase (BTK) inhibitor being developed for the treatment of Non Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia and Multiple Myeloma, all of which are considered hematological malignancies. Pharmacyclics received from Janssen upfront payments totaling $150 million on signing the contract. In addition, Pharmacyclics will receive up to an additional $825 million in development and regulatory milestone payments, based upon continued development progress ($250 million), regulatory progress ($225 million) and approval of the product ($350 million), for total potential upfront and milestone payments of $975 million.

Pharmacyclics and Janssen will collaborate on the development of PCI-32765 for oncology and other indications, excluding inflammation and immune mediated conditions. Each company will lead development for specific indications as stipulated in a global development plan, with development costs shared on a 40/60 basis (Pharmacyclics 40% and Janssen 60%). The agreement includes plans to launch multiple Phase III trials of PCI-32765 over the next several years.

Following regulatory approval, both Pharmacyclics and Janssen will book revenue and co-commercialize PCI-32765. In the US, Pharmacyclics will book sales and take a lead role in US commercial strategy development. Both Pharmacyclics and Janssen will share in commercialization activities. Outside the United States, Janssen will book sales and lead and perform commercialization activities. Profits and losses from the commercialization activities will be split 50/50 on a worldwide basis. Development and commercialization activities under the collaboration will be managed through a shared governance structure.

"We have now formally kicked off our partnership with Janssen for the global development of our BTK inhibitor PCI-32765, and we are extremely pleased with the progress to date. The spirit of cooperation and alignment between the two teams is remarkable, and reaffirms what we believed so strongly when we signed the deal last year that the values of the two companies and their commitment to the potential of PCI-32765 are very much aligned," said Bob Duggan, CEO and Chairman of the Board. "Together we intend to launch broad and aggressive Phase III development programs that will utilize the best of both teams with unwavering focus on our shared mission. This is what patients expect and deserve from us."

Recent Developments & Highlights

Bruton's Tyrosine Kinase (BTK) Inhibitor for Oncology

Results from our Phase Ib/II trial of PCI 32765 in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (PCYC-1102-CA) were presented in an oral presentation at the American Society of Hematology (ASH) Annual Meeting in San Diego, California in December 2011. The trial included a total of 61 patients with relapsed or refractory CLL/SLL enrolled at two dose levels, 420 mg (n=27) or 840 mg (n=34). Oral PCI-32765 was administered daily until disease progression. Data was available from a landmark analysis of 12 months. With a median follow-up of 12.6 months in the 420mg cohort and 9.3 months in the 840mg cohort, the overall response rate (ORR), including PR and CR, for the 420mg dose level was 67% and for the 840 mg dose 68%, as measured by the 2008 International Workshop on Chronic Lymphocytic Leukemia criteria. The responses have been independent of high-risk clinical or genetic features. The estimated landmark 12 month PFS for the pooled cohorts was 86%. The safety profile of PCI-32765 was particularly notable for minimal off target toxicities. The most common treatment related adverse events reported in the trial were Grade 1 (mild) or 2 (moderate) diarrhea, cough, fatigue, and upper respiratory infections, and only 2 of 61 patients have discontinued study treatment due to adverse events regardless of relationship to PCI-32765. The company anticipates having further information on the development of a Phase III program of PCI-32765 in relapsed or refractory CLL/SLL patients in the second quarter of calendar 2012.

Results from our Phase II trial of PCI 32765 in patients with relapsed or refractory mantle cell lymphoma (PCYC-1104-CA) were also presented in an oral presentation at the ASH Annual Meeting in December 2011. The interim analysis included a total of 68 patients accrued to this Phase II trial. PCI-32765 was administered orally at 560 mg daily until disease progression. 51 patients (31 patients had bortezomib-naïve disease, 20 patients had previously received bortezomib) had post-baseline tumor assessments and were thus evaluable for response. The ORR, according to the 2007 Non-Hodgkin's Lymphoma International Working Group criteria, was 69% (35/51 patients). ORR was similar in bortezomib-naïve and bortezomib-exposed patients (71% and 65%, respectively). At the time of this analysis 31 of 35 (89%) responding patients have ongoing responses with the median follow-up of 3.7 months. Consistent with previous trials of PCI-32765, the most common adverse events reported in this trial were Grade 1 (mild) or 2 (moderate) fatigue, diarrhea and nausea. Only 3 of 68 patients discontinued study treatment due to adverse events regardless of relationship to PCI-32765. The company anticipates having further information on the development of a Phase III program of PCI-32765 as a single agent in previously treated mantle cell patients in the second quarter of calendar 2012.

As of the end of December 2011 we enrolled approximately 400 patients into clinical trials evaluating PCI-32765. The ongoing Phase I/II program currently includes the following studies:

• PCYC-04753: A Phase I of PCI-32765 in patients with recurrent B-cell malignancies. This study was designed to assess the safety and tolerability of PCI-32765. Patient enrollment is completed with 66 patients enrolled in the main portion of the study. Enrollment into the diffuse large B-cell lymphoma (DLBCL) activated B-cell (ABC) investigator-led cohort is still ongoing with the National Cancer Institute.
• PCYC-1102-CA: A multicenter, open-label, single agent Phase Ib/II study of PCI-32765 in subjects with relapsed/ refractory or with treatment-naïve (65 years of age or older) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This study was designed to assess safety, tolerability, and efficacy of PCI-32765. Patient enrollment is complete, with 117 patients enrolled. An update on the relapsed or refractory patients treated on this trial was provided at the American Society of Hematology Annual Meeting in December of 2011. We intend to report an interim analysis of elderly treatment naïve patients at one of the upcoming scientific conferences mid-year 2012.
• PCYC-1104-CA: A multicenter, Phase II study of PCI-32765 in patients with relapsed or refractory mantle cell lymphoma, including cohorts of subjects either previously treated with bortezomib or naïve to bortezomib treatment. This trial is active in several US and European sites and, as of the end of December 2011, had enrolled 95 patients. An interim report on this trial was provided at the American Society of Hematology Annual Meeting in December of 2011. We anticipate to complete enrollment of this trial in the first half of calendar 2012 and will report on updated study results thereafter.
• PCYC-1106-CA: A multicenter, open-label, Phase II study of PCI 32765 in subjects with relapsed or refractory DLBCL. This study is designed to assess the activity of PCI-32765 in two genetically distinct subtypes of DLBCL, the activated B-cell (ABC) subtype and the germinal center (GC) subtype. This trial is active in several US sites and, as of the end of December 2011, had enrolled 30 patients. We expect to complete enrollment of all 60 patients within the first half of calendar 2012.
• PCYC-1108-CA: A Phase Ib, multicenter, open-label, study of PCI 32765, in combination with bendamustine and rituximab (BR) in subjects with relapsed or refractory CLL or SLL. This trial completed enrollment with 30 patients. We intend to report an interim analysis of these patients at one of the upcoming scientific conferences mid-year 2012.
• PCYC-1109-CA: A Phase Ib/II study of PCI-32765 in combination with ofatumumab in subjects with relapsed or refractory CLL or SLL is ongoing and enrolled 47 patients as of the end of December 2011. This trial has been expanded and will now enroll up to 70 patients and we are expecting to complete enrollment within the first half of 2012. We intend to report data from a subset of these patients at one of the upcoming scientific conferences mid-year 2012.
• PCYC-1111-CA: A Phase II study of PCI-32765 in subjects with relapsed/refractory multiple myeloma (MM) is on track to start enrolling patients in Q1 of calendar 2012. Pre-clinical studies, both internally as well as through external collaborations, have suggested a potentially vital role of BTK in both malignant plasma cells and osteoclasts, which are involved in bone complications of this disease. The MM trial is expected to enroll 35 patients and we anticipate completing the enrollment by early 2013.

Factor VIIa (FVIIa) Inhibitor

A multicenter Phase I/II of PCI-27483 in patients with locally advanced or metastatic pancreatic cancer that are either receiving or are planned to receive gemcitabine therapy is currently ongoing. The Phase II portion of the study is enrolling and patients are being randomized to receive either gemcitabine alone or gemcitabine plus PCI-27483. The objectives are to assess the safety of FVIIa Inhibitor PCI-27483 at pharmacologically active dose levels, to assess potential inhibition of tumor progression and to obtain initial information of the effects on the incidence of thromboembolic events. This trial is active in several US sites and by the end of December 2011 enrolled 28 patients. Due to a paradigm shift in the use of gemcitabine alone for the treatment of pancreatic cancer enrolling patients onto this randomized study has been challenging. An interim analysis of the results of a subset of the patients enrolled is planned for the first half of calendar 2012.

Histone Deacetylase (HDAC) Inhibitor

Abexinostat (aka PCI-24781) is an oral histone deacetylase inhibitor that is being evaluated in multiple clinical trials by Pharmacyclics and our ex-US collaboration partner, Les Laboratoires Servier (Servier) with approximately 250 patients treated by the end of calendar 2011. Pharmacyclics has completed 2 Phase I studies using abexinostat as a single agent in patients with advanced solid tumors, and is currently conducting a Phase I/II trial in sarcoma patients (in combination with doxorubicin, an anti-tumor agent) and a Phase I/II trial testing abexinostat single agent in patients with relapsed or refractory Non-Hodgkin's lymphoma (NHL). In the sarcoma trial, co-sponsored by the Massachusetts General Hospital and Dana-Farber Cancer Institute, the Phase I dose escalation has been completed and the maximum tolerated dose in combination with doxorubicin has been established. The Phase II portion is currently being planned. In the single agent NHL trial, we are enrolling patients in a Phase II follicular lymphoma arm and expect to complete enrollment by the end of Q1 of calendar 2012. Our collaboration partner for ex-US markets, Servier has expanded its clinical development program of abexinostat and currently has six Phase I/II trials ongoing in Europe in lymphomas and solid tumors with abexinostat as single agent and in combination with radiation as well as other therapeutic agents. The Phase II portion of Servier's single agent lymphoma trial was opened in Q4 of calendar 2011 and is currently enrolling patients. Further analysis of these trials and any updates will be released by Servier.

Conference Call and Webcast Details

Based on timelines of occurring events and availability of our key executives due to travel arrangements, a conference call to update our investors is anticipated to occur in the first week of March.

For further questions please contact Ramses Erdtmann, VP Finance at: 408-215-3325

Use of Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including operating and other expenses adjusted to exclude certain non-cash and non-recurring expenses. These measures are not in accordance with, or an alternative to generally accepted accounting principles, or GAAP, and may be different from non-GAAP financial measures used by other companies. The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are employee related non-cash expenses and the net amount of the therapeutic discovery project tax grant. We believe the presentation of non-GAAP financial measures provides useful information to management and investors regarding various financial and business trends relating to our financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of our ongoing operating performance. In addition, these non-GAAP financial measures are among those indicators we use as a basis for evaluating operational performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. To the extent this release contains historical non-GAAP financial measures, we have also provided corresponding GAAP financial measures for comparative purposes. Reconciliation between certain GAAP and non-GAAP measures is provided below.

About Pharmacyclics

Pharmacyclics® is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune mediated diseases. Our mission and goal is to build a viable biopharmaceutical company that designs, develops and commercializes novel therapies intended to improve quality of life, increase duration of life and resolve serious unmet medial healthcare needs; and to identify promising product candidates based on scientific development expertise, develop our products in a rapid, cost-efficient manner and pursue commercialization and/or development partners when and where appropriate.

Presently, Pharmacyclics has three product candidates in clinical development and several preclinical molecules in lead optimization. We are committed to high standards of ethics, scientific rigor, and operational efficiency as we move each of these programs to viable commercialization.

The Company is headquartered in Sunnyvale, California and is listed on NASDAQ under the symbol PCYC. To learn more about how Pharmacyclics advances science to improve human healthcare visit us at http://www.pharmacyclics.com.

NOTE: This announcement may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding our expectations and beliefs regarding our future results or performance. Because these statements apply to future events, they are subject to risks and uncertainties. When used in this announcement, the words "anticipate", "believe", "estimate", "expect", "expectation", "should", "would", "project", "plan", "predict", "intend" and similar expressions are intended to identify such forward-looking statements. Our actual results could differ materially from those projected in the forward-looking statements. Additionally, you should not consider past results to be an indication of our future performance. For a discussion of the risk factors and other factors that may affect our results, please see the Risk Factors section of our filings with the Securities and Exchange Commission, including our annual report on Form 10-K and quarterly reports on Form 10-Q. We do not intend to update any of the forward-looking statements after the date of this announcement to conform these statements to actual results, to changes in management's expectations or otherwise, except as may be required by law.

Pharmacyclics, Inc. Condensed Consolidated Balance Sheets (unaudited; in thousands)
		December 31, 2011		June 30, 2011
ASSETS
Cash, cash equivalents and marketable securities*	$	240,330	$	112,329
Other current assets		4,552		2,367
Total current assets		244,882		114,696
Property and equipment, net		2,528		1,312
Other assets		344		344
Total assets	$	247,754	$	116,352
LIABILITIES AND STOCKHOLDERS' EQUITY
Deferred revenue – current portion	$	8,041	$	7,000
Other current liabilities		14,404		7,268
Total current liabilities		22,445		14,268
Deferred revenue – non-current portion		71,174		-
Deferred rent		547		410
Total liabilities		94,166		14,678
Stockholders' equity		153,588		101,674
Total liabilities and stockholders' equity	$	247,754	$	116,352
* Marketable securities	$	10,116	$	24,572

Pharmacyclics, Inc. Condensed Consolidated Statements of Operations (unaudited; in thousands, except per share data)
		Three Months Ended December 31,				Six Months Ended December 31,
		2011		2010		2011		2010
Revenues:
License and milestone revenues	$	77,605	$	1,386	$	77,605	$	2,773
Collaboration services revenues		298		1,438		335		2,015
Total revenues		77,903		2,824		77,940		4,788
Operating expenses*:
Research and development		12,076		8,256		23,324		15,958
General and administrative		3,944		2,093		7,294		3,927
Total operating expenses		16,020		10,349		30,618		19,885
Income (loss) from operations		61,883		(7,525)		47,322		(15,097)
Interest and other income (expense), net		21		26		44		75
Income (loss) before income taxes		61,904		(7,499)		47,366		(15,022)
Income tax provision		5,651		-		5,651		-
Net income (loss)	$	56,253	$	(7,499)	$	41,715	$	(15,022)
Net income (loss) per share:
Basic	$	0.82	$	(0.13)	$	0.61	$	(0.25)
Diluted	$	0.78	$	(0.13)	$	0.58	$	(0.25)
Weighted average shares used to compute net income (loss) per share:
Basic		68,658		59,715		68,491		59,497
Diluted		71,725		59,715		71,312		59,497
* Includes share-based compensation as follows:
Research and development	$	1,701	$	1,267	$	3,239	$	2,961
General and administrative		675		671		1,301		1,149
Total	$	2,376	$	1,938	$	4,540	$	4,110

Reconciliation of Selected GAAP Measures to Non-GAAP Measures (1) (unaudited; in thousands, except per share data
		Three Months Ended December 31,
		2011		2010
GAAP net income (loss)	$	56,253	$	(7,499)
Adjustments:
Research & development share-based compensation(2)		1,701		1,267
General & administrative share-based compensation(2)		675		671
Therapeutic discovery project tax grant, net(3)		-		(586)
		2,376		1,352
Non-GAAP net income (loss)	$	58,629	$	(6,147)
Non-GAAP diluted net income (loss) per share	$	0.82	$	(0.10)

(1)	This presentation includes non-GAAP measures. Our non-GAAP measures are not meant to be considered in isolation or as a substitute for comparable GAAP measures and should be read only in conjunction with our financial statements prepared in accordance with GAAP.
(2)	All share-based compensation was excluded for the non-GAAP analysis.
(3)	Represents the therapeutic discovery project tax grant, net of related expenses.

Reconciliation of Selected GAAP Measures to Non-GAAP Measures (1) (unaudited; in thousands, except per share data)
		Six Months Ended December 31,
		2011		2010
GAAP net income (loss)	$	41,715	$	(15,022)
Adjustments:
Research & development share-based compensation(2)		3,239		2,961
General & administrative share-based compensation(2)		1,301		1,149
Therapeutic discovery project tax grant, net(3)		-		(586)
		4,540		3,524
Non-GAAP net income (loss)	$	46,255	$	(11,498)
Non-GAAP diluted net income (loss) per share	$	0.65	$	(0.19)

(1)	This presentation includes non-GAAP measures. Our non-GAAP measures are not meant to be considered in isolation or as a substitute for comparable GAAP measures and should be read only in conjunction with our financial statements prepared in accordance with GAAP.
(2)	All share-based compensation was excluded for the non-GAAP analysis.
(3)	Represents the therapeutic discovery project tax grant, net of related expenses.

SOURCE Pharmacyclics, Inc.

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